MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Current Opinion in Structural Biology' source. Thu, 09 Feb 2012 14:32:05 +0100 http://www.medworm.com/index.php?rid=5620255&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22261637%26dopt%3DAbstract Authors: Phillips SE, Luger K PMID: 22261637 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5620255 Tue, 17 Jan 2012 05:00:00 +0100 5620255 http://www.medworm.com/index.php?rid=5620257&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22257761%26dopt%3DAbstract Authors: Kuper J, Kisker C Abstract Nucleotide excision repair (NER) is a highly versatile DNA repair process. Its ability to repair a large number of different damages with the same subset of recognition factors requires structural tools for damage recognition that are both broad and very accurate. Over the past few years detailed structural information on damage recognition factors from eukaryotic and prokaryotic NER has emerged. These structures shed light on the toolkit utilized in the damage recognition process and help explain the broad substrate specificity of NER. PMID: 22257761 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5620257 Mon, 16 Jan 2012 05:00:00 +0100 5620257 http://www.medworm.com/index.php?rid=5620256&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22257762%26dopt%3DAbstract Authors: Best RB Abstract Theory and experiment have provided answers to many of the fundamental questions of protein folding; a remaining challenge is an accurate, high-resolution picture of folding mechanism. Atomistic molecular simulations with explicit solvent are the most promising method for providing this information, by accounting more directly for the physical interactions that stabilize proteins. Although simulations of folding with such force fields are extremely challenging, they have become feasible as a result of recent advances in computational power, accuracy of the energy functions or 'force fields', and methods for improving sampling of folding events. I review the recent progress in these areas, and highlight future challenges and questions that we may hope to ad... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5620256 Mon, 16 Jan 2012 05:00:00 +0100 5620256 http://www.medworm.com/index.php?rid=5533027&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172540%26dopt%3DAbstract Authors: Killian JL, Li M, Sheinin MY, Wang MD Abstract As the fundamental packing units of DNA in eukaryotes, nucleosomes play a central role in governing DNA accessibility in a variety of cellular processes. Our understanding of the mechanisms underlying this complex regulation has been aided by unique structural and dynamic perspectives offered by single molecule techniques. Recent years have witnessed remarkable advances achieved using these techniques, including the generation of a detailed histone-DNA energy landscape, elucidation of nucleosome disassembly processes, and real-time monitoring of molecular motors interacting with nucleosomes. These and other highlights of single molecule nucleosome studies will be discussed in this review. PMID: 22172540 [PubMed - as suppli... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5533027 Tue, 13 Dec 2011 05:00:00 +0100 5533027 http://www.medworm.com/index.php?rid=5533028&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22169085%26dopt%3DAbstract Authors: White MF, Dillingham MS Abstract Several unexpected reports of iron-sulphur clusters in nucleic acid binding proteins have recently appeared in the literature. Once thought to be relatively rare in these systems, iron-sulphur clusters are now known to be essential components of diverse nucleic acid processing machinery including glycosylases, primases, helicases, nucleases, transcription factors, RNA polymerases and RNA methyltransferases. In many cases, the function of the cluster is poorly understood and crystal structures of these iron-sulphur enzymes reveal little in common between them. In this article, we review the recent developments in the field and discuss to what extent there might exist common mechanistic roles for iron-sulphur clusters in nucleic acid enzymes.... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5533028 Mon, 12 Dec 2011 05:00:00 +0100 5533028 http://www.medworm.com/index.php?rid=5533032&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154606%26dopt%3DAbstract Authors: Rubinson EH, Eichman BF Abstract Protein domains constructed from tandem α-helical repeats have until recently been primarily associated with protein scaffolds or RNA recognition. Recent crystal structures of human mitochondrial termination factor MTERF1 and Bacillus cereus alkylpurine DNA glycosylase AlkD bound to DNA revealed two new superhelical tandem repeat architectures capable of wrapping around the double helix in unique ways. Unlike DNA sequence recognition motifs that rely mainly on major groove read-out, MTERF and ALK motifs locate target sequences and aberrant nucleotides within DNA by resculpting the double-helix through extensive backbone contacts. Comparisons between MTERF and ALK repeats, together with recent advances in ssRNA recognition by Pumilio/FBF (P... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5533032 Fri, 09 Dec 2011 05:00:00 +0100 5533032 http://www.medworm.com/index.php?rid=5533031&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155178%26dopt%3DAbstract Authors: Sekine SI, Tagami S, Yokoyama S Abstract DNA-dependent RNA polymerase (RNAP) is responsible for cellular gene transcription. Although crystallographic studies on prokaryotic and eukaryotic RNAPs have elucidated the basic RNAP architectures, the structural details of many essential events during transcription initiation, elongation, and termination are still largely unknown. Recent crystallographic studies on a bacterial RNAP and yeast RNAP II have revealed different RNAP structural states from that of the normal transcribing complex, as well as the basis of transcription factor functions, advancing our understanding of transcription. These studies have highlighted unexpected similarities in many fundamental aspects of transcription mechanisms between the bacterial and euka... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5533031 Fri, 09 Dec 2011 05:00:00 +0100 5533031 http://www.medworm.com/index.php?rid=5533030&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155179%26dopt%3DAbstract Authors: Guo M, Schimmel P Abstract Proteins are precisely assembled with amino acids by matching the anticodons of charged transfer RNAs to nucleotide triplets in mRNA sequences. Accurate translation depends on the specific coupling of cognate amino acids and tRNAs - a step carried out by aminoacyl-tRNA synthetases (aaRSs) and that generates the genetic code. Owing to their intrinsic similarity, aaRSs developed highly differentiated structures to discriminate between amino acids at the active site for aminoacylation. Because this discrimination is not sufficient to prevent toxic mistranslation, aaRSs developed separate structures to further refine recognition by proofreading. From comprehensive structural studies on aaRSs, many of the molecular details have been elucidated for the... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5533030 Fri, 09 Dec 2011 05:00:00 +0100 5533030 http://www.medworm.com/index.php?rid=5533029&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155180%26dopt%3DAbstract Authors: Pastore A, Temussi PA Abstract Protein aggregation constitutes a constant threat for the living cell as is demonstrated by the several pathologies in which the mechanisms to prevent it fail. It is therefore a question of increasing importance to understand in detail the defence strategies. Here we discuss how molecular interactions can represent a general strategy to prevent aggregation. This view generalizes the more specific paradigm that suggests a competition between folding and aggregation, and allows to include both intrinsically unfolded proteins and proteins that aggregate also under native conditions. We analyze the factors that influence the balance between the two competing pathways and suggest new perspectives to increase our understanding of misfolding patholo... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5533029 Fri, 09 Dec 2011 05:00:00 +0100 5533029 http://www.medworm.com/index.php?rid=5533033&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22153351%26dopt%3DAbstract Authors: Schumacher MA Abstract The accurate segregation or partition of replicated DNA is essential for ensuring stable genome transmission. Partition of bacterial plasmids requires only three elements: a centromere-like DNA site and two proteins, a partition NTPase, and a centromere-binding protein (CBP). Because of this simplicity, partition systems have served as tractable model systems to study the fundamental molecular mechanisms required for DNA segregation at an atomic level. In the last few years, great progress has been made in this endeavor. Surprisingly, these studies have revealed that although the basic partition components are functionally conserved between three types of plasmid partition systems, these systems employ distinct mechanisms of DNA segregation. This rev... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5533033 Tue, 06 Dec 2011 05:00:00 +0100 5533033 http://www.medworm.com/index.php?rid=5533035&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22142589%26dopt%3DAbstract Authors: Noble M, Ladbury JE PMID: 22142589 [PubMed - in process] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5533035 Thu, 01 Dec 2011 05:00:00 +0100 5533035 http://www.medworm.com/index.php?rid=5533034&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22142590%26dopt%3DAbstract Authors: Leonard TA, Hurley JH Abstract Membranes are sites of intense signaling activity within the cell, serving as dynamic scaffolds for the recruitment of signaling molecules and their substrates. The specific and reversible localization of these signaling molecules to membranes is critical for the appropriate activation of downstream signaling pathways. Phospholipid-binding domains, including C1, C2, PH, and PX domains, play critical roles in the membrane targeting of protein kinases. Recent structural studies have identified a new membrane association domain, the Kinase Associated 1 (KA1) domain, which targets a number of yeast and mammalian protein kinases to membranes containing acidic phospholipids. Despite an abundance of localization studies on lipid-binding proteins and... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5533034 Thu, 01 Dec 2011 05:00:00 +0100 5533034 http://www.medworm.com/index.php?rid=5474214&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22129832%26dopt%3DAbstract Authors: Kiefhaber T, Bachmann A, Jensen KS Abstract Protein folding coupled to binding of a specific ligand is frequently observed in biological processes. In recent years numerous studies have addressed the structural properties of the unfolded proteins in the absence of their ligands. Surprisingly few time-resolved investigations on coupled folding and binding reactions have been published up to date and the dynamics and kinetic mechanisms of these processes are still only poorly understood. Especially, it is still unsolved for most systems which conformation of the protein is recognized by the ligand (conformational selection vs. folding-after-binding) and whether the ligand influences the folding kinetics. Here we review experimental methods, kinetic models and time-resolved e... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5474214 Mon, 28 Nov 2011 05:00:00 +0100 5474214 http://www.medworm.com/index.php?rid=5455192&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22104965%26dopt%3DAbstract Authors: Haran G Abstract Unfolded proteins under strongly denaturing conditions are highly expanded. However, when the conditions are more close to native, an unfolded protein may collapse to a compact globular structure distinct from the folded state. This transition is akin to the coil-globule transition of homopolymers. Single-molecule FRET experiments have been particularly conducive in revealing the collapsed state under conditions of coexistence with the folded state. The collapse can be even more readily observed in natively unfolded proteins. Time-resolved studies, using FRET and small-angle scattering, have shown that the collapse transition is a very fast event, probably occurring on the submicrosecond time scale. The forces driving collapse are likely to involve both hy... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5455192 Fri, 18 Nov 2011 05:00:00 +0100 5455192 http://www.medworm.com/index.php?rid=5455193&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100111%26dopt%3DAbstract Authors: Henzler-Wildman K Abstract The small multidrug resistance transporters represent a unique model system for studying the mechanism of secondary active transport and membrane protein evolution. However, this seemingly simple protein has been highly controversial. Recent studies have provided experimental evidence that EmrE exists as an asymmetric dimer that exchanges between identical inward-facing and outward-facing states. Re-examination of the published literature in light of these findings fills in many details of the microscopic steps in the transport cycle. Future work will need to examine how the symmetry observed in vitro affects EmrE function in the asymmetric environment of its native Escherichia coli membrane. PMID: 22100111 [PubMed - as supplied by publisher]... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5455193 Wed, 16 Nov 2011 05:00:00 +0100 5455193 http://www.medworm.com/index.php?rid=5418853&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079548%26dopt%3DAbstract Authors: Cramer P, Wolberger C PMID: 22079548 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5418853 Fri, 11 Nov 2011 05:00:00 +0100 5418853 http://www.medworm.com/index.php?rid=5418854&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056613%26dopt%3DAbstract Authors: Khorasanizadeh S Abstract Histone tails undergo methylation at their lysines and arginines. These chemical marks act as traffic signals that direct activity of chromatin remodeling complexes to appropriate regions of the genome. A surprisingly diverse group of effector protein modules in chromatin remodeling complexes and their associated factors are involved in the recognition of histone methyllysines. Previous studies generally painted a picture of individual lysines recognized by these protein modules in a 1:1 fashion. However, recent structural studies show more complex interactions where the critical lysines are recognized in pairs, or in the context of nucleosomal DNA, or within the central pore of repeat motifs. These interactions extend our understanding of how his... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5418854 Fri, 04 Nov 2011 04:00:00 +0100 5418854 http://www.medworm.com/index.php?rid=5418855&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22054910%26dopt%3DAbstract Authors: Hondele M, Ladurner AG Abstract Histones are highly positively charged proteins that wrap our genome. Their surface properties also make them prone to nonspecific interactions and aggregation. A class of proteins known as histone chaperones is dedicated to safeguard histones by aiding their proper incorporation into nucleosomes. Histone chaperones facilitate ordered nucleosome assembly and disassembly reactions through the formation of semi-stable histone-chaperone intermediates without requiring ATP, but merely providing a complementary protein surface for histones to dynamically interact with. Recurrent 'chaperoning' mechanisms involve the masking of the histone's positive charge and the direct blocking of crucial histone surface sites, including those required for H3-H4... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5418855 Wed, 02 Nov 2011 04:00:00 +0100 5418855 http://www.medworm.com/index.php?rid=5379185&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22040801%26dopt%3DAbstract Authors: Leschziner AE Abstract ATP-dependent chromatin remodeling complexes, or remodelers, are large protein assemblies that use the energy from ATP hydrolysis to non-covalently modify the structure of nucleosomes, playing a central role in the regulation of chromatin dynamics. Our understanding of the mechanism and regulation of this remodeling activity and the diversity of products that chromatin remodelers can generate remains limited, partly because very little structural data are available on these challenging samples. Electron microscopy (EM) and single-particle approaches have made inroads into the structural characterization of a number of remodeling complexes. Here I will review the work done to date, focusing on functional insights we have gained from these structures. ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5379185 Sat, 29 Oct 2011 04:00:00 +0100 5379185 http://www.medworm.com/index.php?rid=5379186&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22036833%26dopt%3DAbstract Authors: Oates J, Watts A Abstract The membrane bilayer has a significant influence over the proteins embedded within it. G protein-coupled receptors (GPCRs) form a large group of membrane proteins with a vast array of critical functions, and direct and indirect interactions with the bilayer are thought to control various essential aspects of receptor function. The presence of cholesterol, in particular, has been the focus of a number of recent studies, with varying receptor-dependent effects reported. However, the possibility of specific cholesterol binding sites on GPCRs remains debatable at present. A deeper structural and mechanistic understanding of the complex and delicately balanced nature of GPCR-bilayer interactions has only been revealed so far in studies with the non-lig... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5379186 Fri, 28 Oct 2011 04:00:00 +0100 5379186 http://www.medworm.com/index.php?rid=5379187&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22036065%26dopt%3DAbstract Authors: Trempe JF Abstract Polyubiquitin chains are assembled through the formation of an isopeptide bond between a lysine side-chain or terminal amino group of a proximal ubiquitin moiety and the carboxy-terminal of a distal ubiquitin moiety. Protein substrates tagged by polyubiquitin chains of different linkages undergo different fates. Many polyubiquitin chain types have been characterized so far, notably Lys11, Lys48, Lys63 and linear chains. These different types of chains are synthesized, disassembled and recognized by selective enzymes and receptors. Here I survey the structural basis for the selective binding of polyubiquitin chains of specific linkages, with an emphasis on recent advances in our understanding of polyubiquitin chain structure and functions. Recent work sug... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5379187 Thu, 27 Oct 2011 04:00:00 +0100 5379187 http://www.medworm.com/index.php?rid=5360863&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22030386%26dopt%3DAbstract Authors: Bycroft M Abstract Eukaryotic DNA is packaged into chromatin, a complex assembly of protein and nucleic acid. The histones within chromatin undergo extensive, highly regulated post-translational modification. One of the main functions of these modifications is to act as markers that ensure that the mutiprotein complexes that regulate the transcription, replication and repair of DNA are directed to the correct region of the genome at the appropriate time. This review focuses on recent biochemical and structural studies on how histones modified by acetylation, ubiquitination, phosphorylation and poly-ADP-ribosylation are recognized. PMID: 22030386 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5360863 Mon, 24 Oct 2011 04:00:00 +0100 5360863 http://www.medworm.com/index.php?rid=5360862&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22030387%26dopt%3DAbstract Authors: Arold ST Abstract Focal adhesion kinase (FAK) has an astonishing number of ligands and functions, which enable it to contribute to embryonic development and human health. FAK can promote different effects in similar cellular environments or similar effects in different cellular environments. Recent advances in structural and cellular analysis of FAK are starting to reveal the interrelationships between the conformations, localizations, interactions, and functions of FAK. This review focuses on our emerging understanding of how the structural framework of FAK mechanistically allows it to integrate manifold stimuli into environment-specific functions. PMID: 22030387 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5360862 Mon, 24 Oct 2011 04:00:00 +0100 5360862 http://www.medworm.com/index.php?rid=5360864&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22023828%26dopt%3DAbstract Authors: D'Arcy S, Luger K Abstract Rtt109 (Regulator of Ty1 Transposition 109) is a fungal-specific histone acetyltransferase required for modification of histone H3 K9, K27 and K56. These acetylations are associated with nascent histone H3 and play an integral role in replication-coupled and repair-coupled nucleosome assembly. Rtt109 is unique among acetyltransferases as it is activated by a histone chaperone; either Vps75 (Vacuolar Protein Sorting 75) or Asf1 (Anti-silencing Function 1). Recent biochemical, structural and genetic studies have shed light on the intricacies of this activation. It is now clear that Rtt109-Asf1 acetylates K56, while Rtt109-Vps75 acetylates K9 and K27. This reinforces that Asf1 and Vps75 activate Rtt109 via distinct molecular mechanisms. Structures o... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5360864 Sat, 22 Oct 2011 04:00:00 +0100 5360864 http://www.medworm.com/index.php?rid=5344288&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22014650%26dopt%3DAbstract Authors: Samara NL, Wolberger C Abstract Eukaryotic transcriptional coactivators are multi-subunit complexes that both modify chromatin and recognize histone modifications. Until recently, structural information on these large complexes has been limited to isolated enzymatic domains or chromatin-binding motifs. This review summarizes recent structural studies of the SAGA coactivator complex that have greatly advanced our understanding of the interplay between its different subunits. The structure of the four-protein SAGA deubiquitinating module has provided a first glimpse of the larger organization of a coactivator complex, and illustrates how interdependent subunits interact with each other to form an active and functional enzyme complex. In addition, structures of the histone bi... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5344288 Tue, 18 Oct 2011 04:00:00 +0100 5344288 http://www.medworm.com/index.php?rid=5344289&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21996440%26dopt%3DAbstract Authors: Hauk G, Bowman GD Abstract This review focuses on recent structural insights into regulation and nucleic acid binding of Superfamily 2 (SF2)-type helicases as they relate to chromatin remodelers. We review structural features of the Chd1 chromatin remodeler regarding regulation of the ATPase motor, and discuss related strategies observed for other SF2 ATPases. Since no SWI2/SNF2 ATPases have yet been captured bound to DNA in a state competent for ATP hydrolysis, we turn to structural examples from the DEAD-box RNA helicase family, and suggest that SWI2/SNF2-specific inserts may be poised to alter canonical duplex DNA structure. PMID: 21996440 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5344289 Tue, 11 Oct 2011 04:00:00 +0100 5344289 http://www.medworm.com/index.php?rid=5296187&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21978577%26dopt%3DAbstract Authors: Bowler BE Abstract The denatured state ensemble (DSE) of unfolded proteins, once considered to be well-modeled by an energetically featureless random coil, is now well-known to contain flickering elements of residual structure. The position and nature of DSE residual structure may provide clues toward deciphering the protein folding code. This review focuses on recent advances in our understanding of the nature of DSE collapse under folding conditions, the quantification of the stability of residual structure in the DSE, the determination of the location and types of residues involved in thermodynamically significant residual structure and advances in detection of long-range interactions in the DSE. PMID: 21978577 [PubMed - as supplied by publisher] (Source: Current Op... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5296187 Tue, 04 Oct 2011 04:00:00 +0100 5296187 http://www.medworm.com/index.php?rid=5296186&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21978957%26dopt%3DAbstract Authors: Schwarz F, Aebi M Abstract N-linked glycosylation, a protein modification system present in all domains of life, is characterized by a high structural diversity of N-linked glycans found among different species and by a large number of proteins that are glycosylated. Based on structural, functional, and phylogenetic approaches, this review discusses the highly conserved processes that are at the basis of this unique general protein modification system. PMID: 21978957 [PubMed - in process] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5296186 Sat, 01 Oct 2011 04:00:00 +0100 5296186 http://www.medworm.com/index.php?rid=5276602&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945038%26dopt%3DAbstract Authors: Stalnaker SH, Stuart R, Wells L Abstract Post-translational modification of polypeptides with glycans increases the diversity of the structures of proteins and imparts increased functional diversity. Here, we review the current literature on a relatively new O-glycosylation pathway, the mammalian O-mannosylation pathway. The importance of O-mannosylation is illustrated by the fact that O-mannose glycan structures play roles in a variety of processes including viral entry into cells, metastasis, cell adhesion, and neuronal development. Furthermore, mutations in the enzymes of this pathway are causal for a variety of congenital muscular dystrophies. Here we highlight the protein substrates, glycan structures, and enzymes involved in O-mannosylation as well as our gaps in und... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5276602 Thu, 22 Sep 2011 04:00:00 +0100 5276602 http://www.medworm.com/index.php?rid=5276601&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945039%26dopt%3DAbstract Authors: Haltiwanger RS, Feizi T PMID: 21945039 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5276601 Thu, 22 Sep 2011 04:00:00 +0100 5276601 http://www.medworm.com/index.php?rid=5276600&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945040%26dopt%3DAbstract Authors: Grossman M, Sela-Passwell N, Sagi I Abstract A network of dynamic protein interactions with their protein partners, substrates, and ligands is known to be crucial for biological function. Revealing molecular and structural-based mechanisms at atomic resolution and in real-time is fundamental for achieving a basic understanding of cellular processes. These technically challenging goals may be achieved by combining time-resolved spectroscopic and structural-kinetic tools, thus providing broad insights into specific molecular events over a wide range of timescales. Here we review representative studies utilizing such an integrated real-time structural approach designed to reveal molecular mechanisms underlying protein interactions at atomic resolution. PMID: 21945040 [Pub... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5276600 Thu, 22 Sep 2011 04:00:00 +0100 5276600 http://www.medworm.com/index.php?rid=5246067&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21924891%26dopt%3DAbstract Authors: Rana NA, Haltiwanger RS Abstract The Notch family of receptors plays essential roles in many phases of development, and dysregulation of Notch activity is increasingly recognized as a player in many diseases. O-Glycosylation of the Notch extracellular domain is essential for Notch activity, and tissue-specific alterations in the glycan structures are known to regulate activity. Here we review recent advances in identification and characterization of the enzymes responsible for glycosylating Notch and molecular mechanisms for how these O-glycans affect Notch activity. PMID: 21924891 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5246067 Thu, 15 Sep 2011 04:00:00 +0100 5246067 http://www.medworm.com/index.php?rid=5228463&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21917445%26dopt%3DAbstract The objective is to define common parameters of recognition and to provide a platform for understanding the determinants of specificity. This information could be of use for the prediction of the location of sialic acid binding sites in viruses for which structural information is still lacking. An improved understanding of the principles that govern the recognition of sialic acid and sialylated oligosaccharides would also advance efforts to develop efficient antiviral agents. PMID: 21917445 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5228463 Mon, 12 Sep 2011 04:00:00 +0100 5228463 http://www.medworm.com/index.php?rid=5228462&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21917446%26dopt%3DAbstract Authors: Sharon M, Robinson CV PMID: 21917446 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5228462 Mon, 12 Sep 2011 04:00:00 +0100 5228462 http://www.medworm.com/index.php?rid=5218331&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21889889%26dopt%3DAbstract Authors: Kumar P, Yang M, Haynes BC, Skowyra ML, Doering TL Abstract Cryptococcus neoformans, a basidiomycete yeast and opportunistic pathogen, expends significant biosynthetic effort on construction of a polysaccharide capsule with a radius that may be many times that of the cell. Beyond posing a stimulating challenge in terms of defining biosynthetic pathways, the capsule is required for this yeast to cause fatal disease. This combination has focused the attention of researchers on this system. Here we briefly review two aspects of the rapidly advancing field of capsule synthesis: the extensive variation that occurs in capsule polymers and the regulation of capsule biosynthesis. PMID: 21889889 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5218331 Thu, 01 Sep 2011 04:00:00 +0100 5218331 http://www.medworm.com/index.php?rid=5218332&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21889329%26dopt%3DAbstract Authors: Cullen PJ Abstract Signaling mucins are large transmembrane glycoproteins that regulate signal transduction pathways. Recent advances have shown that two major types of post-translational modifications, protein glycosylation and proteolytic processing, play important and unexpected roles in regulating signaling mucin function. New O-glycosyltransferases and proteases have been identified, and the structure of the domain that undergoes auto-proteolysis has been solved. A picture is beginning to emerge where specific glycosyl modifications and regulated processing control the signaling and adherence properties of signaling glycoproteins and contribute to the routing of signals to specific pathways. PMID: 21889329 [PubMed - as supplied by publisher] (Source: Current Opini... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5218332 Wed, 31 Aug 2011 04:00:00 +0100 5218332 http://www.medworm.com/index.php?rid=5218333&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21880480%26dopt%3DAbstract Authors: Benesch JL, Ruotolo BT Abstract Over the past two decades, mass spectrometry (MS) has emerged as a bone fide approach for structural biology. MS can inform on all levels of protein organization, and enables quantitative assessments of their intrinsic dynamics. The key advantages of MS are that it is a sensitive, high-resolution separation technique with wide applicability, and thereby allows the interrogation of transient protein assemblies in the context of complex mixtures. Here we describe how molecular-level information is derived from MS experiments, and how it can be combined with spatial and dynamical restraints obtained from other structural biology approaches to allow hybrid studies of protein architecture and movements. PMID: 21880480 [PubMed - as supplied by... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5218333 Mon, 29 Aug 2011 04:00:00 +0100 5218333 http://www.medworm.com/index.php?rid=5218335&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21872465%26dopt%3DAbstract Authors: Upadhyay AK, Horton JR, Zhang X, Cheng X Abstract Both components of chromatin (DNA and histones) are subjected to dynamic postsynthetic covalent modifications. Dynamic histone lysine methylation involves the activities of modifying enzymes (writers), enzymes removing modifications (erasers), and readers of the epigenetic code. Known histone lysine demethylases include flavin-dependent monoamine oxidase lysine-specific demethylase 1 and α-ketoglutarate-Fe(II)-dependent dioxygenases containing Jumonji domains. Importantly, the Jumonji domain often associates with at least one additional recognizable domain (reader) within the same polypeptide that detects the methylation status of histones and/or DNA. Here, we summarize recent developments in characterizing structural and ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5218335 Thu, 25 Aug 2011 04:00:00 +0100 5218335 http://www.medworm.com/index.php?rid=5218334&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21872466%26dopt%3DAbstract Authors: Lombardi PM, Cole KE, Dowling DP, Christianson DW Abstract Metal-dependent histone deacetylases (HDACs) catalyze the hydrolysis of acetyl-l-lysine side chains in histone and nonhistone proteins to yield l-lysine and acetate. This chemistry plays a critical role in the regulation of numerous biological processes. Aberrant HDAC activity is implicated in various diseases, and HDACs are validated targets for drug design. Two HDAC inhibitors are currently approved for cancer chemotherapy, and other inhibitors are in clinical trials. To date, X-ray crystal structures are available for four human HDACs (2, 4, 7, and 8) and three HDAC-related deacetylases from bacteria (histone deacetylase-like protein (HDLP); histone deacetylase-like amidohydrolase (HDAH); acetylpolyamine amidohy... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5218334 Thu, 25 Aug 2011 04:00:00 +0100 5218334 http://www.medworm.com/index.php?rid=5174942&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21868214%26dopt%3DAbstract Authors: Endres NF, Engel K, Das R, Kovacs E, Kuriyan J Abstract The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase involved in cell growth that is often misregulated in cancer. Several recent studies highlight the unique structural mechanisms involved in its regulation. Some elucidate the important role that the juxtamembrane segment and the transmembrane helix play in stabilizing the activating asymmetric kinase dimer, and suggest that its activation mechanism is likely to be conserved among the other human EGFR-related receptors. Other studies provide new explanations for two long observed, but poorly understood phenomena, the apparent heterogeneity in ligand binding and the formation of ligand-independent dimers. New insights into the allosteric mechanism... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5174942 Mon, 22 Aug 2011 23:00:00 +0100 5174942 http://www.medworm.com/index.php?rid=5174943&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862320%26dopt%3DAbstract Authors: Alushin G, Nogales E Abstract Kinetochores are large macromolecular assemblies that link chromosomes to spindle microtubules (MTs) during mitosis. Here we review recent advances in the study of core MT-binding kinetochore complexes using electron microcopy methods in vitro and nanometer-accuracy fluorescence microscopy in vivo. We synthesize these findings in novel three-dimensional models of both the budding yeast and vertebrate kinetochore in different stages of mitosis. There is a growing consensus that kinetochores are highly dynamic, supra-molecular machines that undergo dramatic structural rearrangements in response to MT capture and spindle forces during mitosis. PMID: 21862320 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5174943 Fri, 19 Aug 2011 23:00:00 +0100 5174943 http://www.medworm.com/index.php?rid=5141083&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840209%26dopt%3DAbstract Authors: Antonczak AK, Morris J, Tippmann EM Abstract There are many approaches to introduce non-native functionality into proteins either translationally or post-translationally. When a noncanonical amino acid (NAA) is incorporated translationally, the host organism's existing translational machinery is relied upon to insert the amino acid by the same well-established mechanisms used by the host to achieve high fidelity insertion of its canonical amino acids. Research into the in vivo incorporation of NAAs has typically concentrated on evolving or engineering aminoacyl tRNA synthetases (aaRSs); however, new studies have increasingly focused on other members of the translational apparatus, for example entire ribosomes, in attempts to increase the fidelity and efficiency of incorpor... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5141083 Wed, 10 Aug 2011 23:00:00 +0100 5141083 http://www.medworm.com/index.php?rid=5141084&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21831629%26dopt%3DAbstract We described the architecture of the membrane domain and of the entire bacterial complex I. X-ray analysis of the larger mitochondrial enzyme has also been published. The core subunits of the bacterial and mitochondrial enzymes have remarkably similar structures. The proposed mechanism of coupling between electron transfer and proton translocation involves long-range conformational changes, coordinated in part by a long α-helix, akin to the coupling rod of a steam engine. PMID: 21831629 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5141084 Sun, 07 Aug 2011 23:00:00 +0100 5141084 http://www.medworm.com/index.php?rid=5141086&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21824762%26dopt%3DAbstract Authors: Yonath A Abstract X-ray crystallography is the fundamental research tool that shaped our notion on biological structure & function at the molecular level. It generates the information vital to understand life processes by providing the information required for creating accurate three-dimensional models (namely mapping the position of each and every atom that makes up the studied object). The use of this method begun in the middle of last century following Max von Laue discovery of the phenomenon of diffraction of X-rays by crystals, and the successful application of this discovery for the determination of the electronic distribution within simple inorganic molecules by Sir William Henry Bragg and his son, William Lawrence Bragg. The idea of extension of this method to ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5141086 Fri, 05 Aug 2011 23:00:00 +0100 5141086 http://www.medworm.com/index.php?rid=5097430&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21813274%26dopt%3DAbstract Authors: Yahav T, Maimon T, Grossman E, Dahan I, Medalia O Visualization of cellular processes at a resolution of the individual protein should involve integrative and complementary approaches that can eventually draw realistic functional and cellular landscapes. Electron tomography of vitrified but otherwise unaltered cells emerges as a central method for three-dimensional reconstruction of cellular architecture at a resolution of 2-6nm. While a combination of correlative light-based microscopy with cryo-electron tomography (cryo-ET) provides medium-resolution insight into pivotal cellular processes, fitting high-resolution structural approaches, for example, X-ray crystallography, into reconstructed macromolecular assemblies provides unprecedented information on native protein assemb... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5097430 Sun, 31 Jul 2011 23:00:00 +0100 5097430 http://www.medworm.com/index.php?rid=5097487&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21807498%26dopt%3DAbstract Authors: Mancia F, Love J Structural genomics approaches on integral membrane proteins have been postulated for over a decade, yet specific efforts are lagging years behind their soluble counterparts. Indeed, high throughput methodologies for production and characterization of prokaryotic integral membrane proteins are only now emerging, while large-scale efforts for eukaryotic ones are still in their infancy. Presented here is a review of recent literature on actively ongoing structural genomics of membrane protein initiatives, with a focus on those aimed at implementing interesting techniques aimed at increasing our rate of success for this class of macromolecules. PMID: 21807498 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5097487 Fri, 29 Jul 2011 23:00:00 +0100 5097487 http://www.medworm.com/index.php?rid=5097453&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21807499%26dopt%3DAbstract Authors: Chill JH, Naider F Structure determination of membrane-associated proteins (MPs) represents a frontier of structural biology that is characterized by unique challenges in sample preparation and data acquisition. No less important is our ability to study the dynamics of MPs, since MP flexibility and characteristic motions often make sizeable contributions to their function. This review focuses on solution state NMR methods to characterize dynamics of MPs in the membrane environment. NMR approaches to study molecular motions on a wide range of time-scales and their application to membrane proteins are described. Studies of polytopic and bitopic MPs demonstrating the power of such methods to characterize the dynamic behavior of MPs and their interaction with the membrane-mimickin... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5097453 Fri, 29 Jul 2011 23:00:00 +0100 5097453 http://www.medworm.com/index.php?rid=5097496&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21795039%26dopt%3DAbstract Authors: Blundell TL, Hendrickson WA PMID: 21795039 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5097496 Sun, 24 Jul 2011 23:00:00 +0100 5097496 http://www.medworm.com/index.php?rid=5097560&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21782416%26dopt%3DAbstract Authors: Steyaert J, Kobilka BK Remarkable progress has been made in the field of G protein-coupled receptor (GPCR) structural biology during the past four years. Several obstacles to generating diffraction quality crystals of GPCRs have been overcome by combining innovative methods ranging from protein engineering to lipid-based screens and microdiffraction technology. The initial GPCR structures represent energetically stable inactive-state conformations. However, GPCRs signal through different G protein isoforms or G protein-independent effectors upon ligand binding suggesting the existence of multiple ligand-specific active states. These active-state conformations are unstable in the absence of specific cytosolic signaling partners representing new challenges for structural biology... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5097560 Tue, 19 Jul 2011 23:00:00 +0100 5097560 http://www.medworm.com/index.php?rid=5097523&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21782417%26dopt%3DAbstract Authors: Caplan J, Niethammer M, Taylor RM, Czymmek KJ Correlative microscopy is a sophisticated approach that combines the capabilities of typically separate, but powerful microscopy platforms: often including, but not limited, to conventional light, confocal and super-resolution microscopy, atomic force microscopy, transmission and scanning electron microscopy, magnetic resonance imaging and micro/nano CT (computed tomography). When targeting rare or specific events within large populations or tissues, correlative microscopy is increasingly being recognized as the method of choice. Furthermore, this multi-modal assimilation of technologies provides complementary and often unique information, such as internal and external spatial, structural, biochemical and biophysical details from t... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5097523 Tue, 19 Jul 2011 23:00:00 +0100 5097523 http://www.medworm.com/index.php?rid=5051388&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21775127%26dopt%3DAbstract Authors: Cherezov V Lipidic cubic phase (LCP) is a membrane-mimetic matrix suitable for stabilization and crystallization of membrane proteins in lipidic environment. LCP technologies, however, have not been fully embraced by the membrane protein structural biology community, primarily because of the difficulties associated with handling viscous materials. Recent developments of pre-crystallization assays and improvements in crystal imaging, successes in obtaining high resolution structures of G protein-coupled receptors (GPCRs), and commercial availability of LCP tools and instruments are beginning to attract structural biologists to integrate LCP technologies in their research. This wider acceptance should translate to an increased number of otherwise difficult-to-crystallize membran... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5051388 Sun, 17 Jul 2011 23:00:00 +0100 5051388 http://www.medworm.com/index.php?rid=5051387&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21775128%26dopt%3DAbstract Authors: Nietlispach D, Gautier A NMR spectroscopy has established itself as one of the main techniques for the structural study of integral membrane proteins. Remarkably, over the last few years, substantial progress has been achieved in the structure determination of increasingly complex polytopical α-helical membrane proteins, with their size approaching ∼100kDa. Such advances are the result of significant improvements in NMR methodology, sample preparation and powerful selective isotope labelling schemes. We review the requirements facilitating such work based on the more recent solution NMR studies of α-helical proteins. While the majority of such studies still use detergent-solubilized proteins, alternative more native-like lipid-based media are emerging. Recent interaction, ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5051387 Sun, 17 Jul 2011 23:00:00 +0100 5051387 http://www.medworm.com/index.php?rid=5051389&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21767945%26dopt%3DAbstract Authors: Fitzpatrick JA, Lillemeier BF Fluorescence correlation spectroscopy (FCS) is a minimally invasive real-time fluorescence technique capable of detecting single molecules in vitro and in situ. By recording and correlating the fluctuations in fluorescence intensity measurements, it is possible to obtain information on molecular mobility and diffusion, hydrodynamic radii, local concentrations and photochemical and photophysical properties. By using dual-color cross-correlation spectroscopy, it is possible to monitor highly specific molecular-level interactions such as binding processes and chemical reactions. Recent advances in alternative detection schemes have allowed the extension of these techniques to the monitoring of slower timescales (e.g. Raster Image Correlation Spectros... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5051389 Fri, 15 Jul 2011 23:00:00 +0100 5051389 http://www.medworm.com/index.php?rid=5051390&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21764295%26dopt%3DAbstract Authors: Johnston JM, Filizola M Despite many years of dedicated efforts, high-resolution structural determination of membrane proteins lags far behind that of soluble proteins. Computational methods in general, and molecular dynamics (MD) simulations in particular, have represented important alternative resources over the years to advance understanding of membrane protein structure and function. However, it is only recently that much progress has been achieved owing to new high-resolution membrane protein structures, specialized parallel computer architectures, and efficient simulation algorithms. This has definitely been the case for G protein-coupled receptors (GPCRs), which have assumed a leading role in the area of structural biology with several new structures appearing in the li... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5051390 Thu, 14 Jul 2011 23:00:00 +0100 5051390 http://www.medworm.com/index.php?rid=5051391&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763125%26dopt%3DAbstract This article reviews the recent successes of computational protein design techniques applied to integral membrane proteins. This emerging area is still handicapped by significant difficulties in the experimental characterization of the stability and structure of the designed proteins. Nevertheless, by focusing on oligomeric complexes of single-span transmembrane (TM) peptides with detectable activity, the computational design of membrane proteins has already produced very exciting results. The 'take-home message' is that optimization of van der Waals packing and hydrogen bonding (both 'canonical' and weak Cα-H⋯O bonds) can produce functional structures of remarkable stability and specificity in the membrane. PMID: 21763125 [PubMed - as supplied by publisher] (Source: Current Opinion... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5051391 Tue, 12 Jul 2011 23:00:00 +0100 5051391 http://www.medworm.com/index.php?rid=5051392&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21752635%26dopt%3DAbstract Authors: Fromme P, Spence JC The invention of free electron X-ray lasers has opened a new era for membrane protein structure determination with the recent first proof-of-principle of the new concept of femtosecond nanocrystallography. Structure determination is based on thousands of diffraction snapshots that are collected on a fully hydrated stream of nanocrystals. This review provides a summary of the method and describes how femtosecond X-ray crystallography overcomes the radiation-damage problem in X-ray crystallography, avoids the need for growth and freezing of large single crystals while offering a new method for direct digital phase determination by making use of the fully coherent nature of the X-ray beam. We briefly review the possibilities for time-resolved crystallography, ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5051392 Sun, 10 Jul 2011 23:00:00 +0100 5051392 http://www.medworm.com/index.php?rid=5000846&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723721%26dopt%3DAbstract Authors: Deupi X, Standfuss J Recent years have seen tremendous breakthroughs in structure determination of G-protein-coupled receptors (GPCRs). In 2011, two agonist-bound active-state structures of rhodopsin have been published. Together with structures of several rhodopsin activation intermediates and a wealth of biochemical and spectroscopic information, they provide a unique structural framework on which to understand GPCR activation. Here we use this framework to compare the recent crystal structures of the agonist-bound active states of the β(2) adrenergic receptor (β(2)AR) and the A(2A) adenosine receptor (A(2A)AR). While activation of these three GPCRs results in rearrangements of TM5 and TM6, the extent of this conformational change varies considerably. Displacements of the ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5000846 Wed, 29 Jun 2011 23:00:00 +0100 5000846 http://www.medworm.com/index.php?rid=5000847&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21719274%26dopt%3DAbstract Authors: Fairman JW, Noinaj N, Buchanan SK The outer membranes of Gram-negative bacteria, mitochondria, and chloroplasts all contain transmembrane β-barrel proteins. These β-barrel proteins serve essential functions in cargo transport and signaling and are also vital for membrane biogenesis. They have also been adapted to perform a diverse set of important cellular functions including acting as porins, transporters, enzymes, virulence factors and receptors. Recent structures of transmembrane β-barrels include that of a full length autotransporter (EstA), a bacterial heme transporter complex (HasR), a bacterial porin in complex with several ligands (PorB), and the mitochondrial voltage-dependent anion channel (VDAC) from both mouse and human. These represent only a few of the interes... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5000847 Mon, 27 Jun 2011 23:00:00 +0100 5000847 http://www.medworm.com/index.php?rid=5000848&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21703846%26dopt%3DAbstract Authors: Konermann L, Pan Y, Stocks BB Deciphering the mechanisms of protein folding remains a considerable challenge. In this review we discuss the application of pulsed oxidative labeling for tracking protein structural changes in a time-resolved fashion. Exposure to a microsecond OH pulse at selected time points during folding induces the oxidation of solvent-accessible side chains, whereas buried residues are protected. Oxidative modifications can be detected by mass spectrometry. Folding is associated with dramatic accessibility changes, and therefore this method can provide detailed mechanistic insights. Solvent accessibility patterns are complementary to H/D exchange investigations, which report on the extent of hydrogen bonding. This review highlights the application of pulsed ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=5000848 Tue, 21 Jun 2011 23:00:00 +0100 5000848 http://www.medworm.com/index.php?rid=4955188&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21684149%26dopt%3DAbstract Authors: Verschueren E, Vanhee P, van der Sloot AM, Serrano L, Rousseau F, Schymkowitz J Structure-based computational methods are popular tools for designing proteins and interactions between proteins because they provide the necessary insight and details required for rational engineering. Here, we first argue that large-scale databases of fragments contain a discrete but complete set of building blocks that can be used to design structures. We show that these structural alphabets can be saturated to provide conformational ensembles that sample the native structure space around energetic minima. Second, we show that catalogs of interaction patterns hold the key to overcome the lack of scaffolds when computationally designing protein interactions. Finally, we illustrate the power of da... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4955188 Wed, 15 Jun 2011 23:00:00 +0100 4955188 http://www.medworm.com/index.php?rid=4955187&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21684150%26dopt%3DAbstract Authors: Dalby PA Directed evolution is widely used to improve enzymes, particularly for industrial biocatalytic processes. Molecular biology advances present many new strategies for directed evolution. Commonly used techniques have led to many successful examples of enzyme improvement, yet there is still a need to improve both the efficiency and capability of directed evolution. Recent strategies aimed at making directed evolution faster and more efficient take better advantage of available structural and sequence information. The underlying principles that lead to early dead-ends for directed evolution experiments are also discussed along with recent strategies designed to by-pass them. Several emerging methods for creating novel enzymes are also discussed including examples of catal... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4955187 Wed, 15 Jun 2011 23:00:00 +0100 4955187 http://www.medworm.com/index.php?rid=4855896&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21601443%26dopt%3DAbstract Authors: Dhamankar H, Prather KL The dwindling nature of petroleum and other fossil reserves has provided impetus towards microbial synthesis of fuels and value added chemicals from biomass-derived sugars as a renewable resource. Microbes have naturally evolved enzymes and pathways that can convert biomass into hundreds of unique chemical structures, a property that can be effectively exploited for their engineering into Microbial Chemical Factories (MCFs). De novo pathway engineering facilitates expansion of the repertoire of microbially synthesized compounds beyond natural products. In this review, we visit some recent successes in such novel pathway engineering and optimization, with particular emphasis on the selection and engineering of pathway enzymes and balancing of their acces... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4855896 Wed, 18 May 2011 23:00:00 +0100 4855896 http://www.medworm.com/index.php?rid=4855897&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21600758%26dopt%3DAbstract Authors: Pantazes RJ, Grisewood MJ, Maranas CD Proteins are the molecules cells primarily rely on for catalysis, recognition, signaling, defense, locomotion, and structural integrity. Engineering proteins for improved function or new applications is a fast-growing segment of biotechnology and biomedicine. Experimental efforts based on the screening of large mutant libraries have led to many successes but they do not provide quantitative design principles and/or insight into the structural features that underpin the desired function. The computational de novo design of proteins promises to bridge this gap; however, it requires reliable structure prediction, provisions for protein stability, and accurate descriptions of inter-molecule interactions. Studies that successfully meet all thes... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4855897 Tue, 17 May 2011 23:00:00 +0100 4855897 http://www.medworm.com/index.php?rid=4855898&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21565486%26dopt%3DAbstract Authors: Pyle AM, Shakked Z PMID: 21565486 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4855898 Mon, 09 May 2011 23:00:00 +0100 4855898 http://www.medworm.com/index.php?rid=4804006&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21530234%26dopt%3DAbstract Authors: Fisher CK, Stultz CM The relatively flat energy landscapes associated with intrinsically disordered proteins makes modeling these systems especially problematic. A comprehensive model for these proteins requires one to build an ensemble consisting of a finite collection of structures, and their corresponding relative stabilities, which adequately capture the range of accessible states of the protein. In this regard, methods that use computational techniques to interpret experimental data in terms of such ensembles are an essential part of the modeling process. In this review, we critically assess the advantages and limitations of current techniques and discuss new methods for the validation of these ensembles. PMID: 21530234 [PubMed - as supplied by publisher] (Source: Cur... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4804006 Tue, 26 Apr 2011 23:00:00 +0100 4804006 http://www.medworm.com/index.php?rid=4804005&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21530235%26dopt%3DAbstract Authors: Liberman JA, Wedekind JE Genome sequencing has produced thousands of nonprotein coding (nc)RNA sequences including new ribozymes and riboswitches. Such RNAs are notable for their extraordinary functionality, which entails exquisite folding that culminates in biocatalytic or ligand-binding capabilities. Here we discuss advances in relating ncRNA form to function with an emphasis on base pK(a) shifting by the hairpin and hepatitis delta virus ribozymes. We then describe ligand binding by the two smallest riboswitches, which target preQ(1) and S-adenosyl-(l)-homocysteine, followed by an analysis of a second-messenger riboswitch that binds cyclic-di-GMP. Each riboswitch is then compared to a protein that binds the same ligand to contrast binding properties. The results showcase th... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4804005 Tue, 26 Apr 2011 23:00:00 +0100 4804005 http://www.medworm.com/index.php?rid=4804004&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21530236%26dopt%3DAbstract Authors: Dunker AK, Gough J PMID: 21530236 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4804004 Tue, 26 Apr 2011 23:00:00 +0100 4804004 http://www.medworm.com/index.php?rid=4751821&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21514142%26dopt%3DAbstract Authors: Tompa P It is now generally accepted that many proteins or protein domains (intrinsically disordered proteins, IDPs) lack a well-defined tertiary structure under functional conditions. Due to recent concerted activity, a critical transition in this field is gaining momentum, in which qualitative observations are turned into quantitative structural models of IDPs. Here, it is suggested that the transition is set up by the synergy of: (i) more advanced bioinformatic tools for the prediction of disorder and function of IDPs, (ii) ensemble description of their structure and dynamics in both free and bound states, down to the single molecule level, (iii) advent of in-cell approaches for characterizing their structure and function in vivo, and (iv) generation of small-molecule inhib... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4751821 Tue, 19 Apr 2011 23:00:00 +0100 4751821 http://www.medworm.com/index.php?rid=4751820&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21514143%26dopt%3DAbstract Authors: Laing C, Schlick T RNA molecules are important cellular components involved in many fundamental biological processes. Understanding the mechanisms behind their functions requires RNA tertiary structure knowledge. Although modeling approaches for the study of RNA structures and dynamics lag behind efforts in protein folding, much progress has been achieved in the past two years. Here, we review recent advances in RNA folding algorithms, RNA tertiary motif discovery, applications of graph theory approaches to RNA structure and function, and in silico generation of RNA sequence pools for aptamer design. Advances within each area can be combined to impact many problems in RNA structure and function. PMID: 21514143 [PubMed - as supplied by publisher] (Source: Current Opinion in... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4751820 Tue, 19 Apr 2011 23:00:00 +0100 4751820 http://www.medworm.com/index.php?rid=4751819&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21514144%26dopt%3DAbstract Authors: Babu MM, van der Lee R, de Groot NS, Gsponer J Intrinsically disordered proteins (IDPs) are enriched in signaling and regulatory functions because disordered segments permit interaction with several proteins and hence the re-use of the same protein in multiple pathways. Understanding IDP regulation is important because altered expression of IDPs is associated with many diseases. Recent studies show that IDPs are tightly regulated and that dosage-sensitive genes encode proteins with disordered segments. The tight regulation of IDPs may contribute to signaling fidelity by ensuring that IDPs are available in appropriate amounts and not present longer than needed. The altered availability of IDPs may result in sequestration of proteins through non-functional interactions involving... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4751819 Tue, 19 Apr 2011 23:00:00 +0100 4751819 http://www.medworm.com/index.php?rid=4751818&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21514145%26dopt%3DAbstract Authors: Schlessinger A, Schaefer C, Vicedo E, Schmidberger M, Punta M, Rost B As an operational definition, we refer to regions in proteins that do not adopt regular three-dimensional structures in isolation, as disordered regions. An antipode to disorder would be 'well-structured' rather than 'ordered'. Here, we argue for the following three hypotheses. Firstly, it is more useful to picture disorder as a distinct phenomenon in structural biology than as an extreme example of protein flexibility. Secondly, there are many very different flavors of protein disorder, nevertheless, it seems advantageous to portray the universe of all possible proteins in terms of two main types: well-structured, disordered. There might be a third type 'other' but we have so far no positive evidence for th... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4751818 Tue, 19 Apr 2011 23:00:00 +0100 4751818 http://www.medworm.com/index.php?rid=4751849&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21497083%26dopt%3DAbstract Authors: Bailor MH, Mustoe AM, Brooks CL, Al-Hashimi HM Accompanying recent advances in determining RNA secondary structure is the growing appreciation for the importance of relatively simple topological constraints, encoded at the secondary structure level, in defining the overall architecture, folding pathways, and dynamic adaptability of RNA. A new view is emerging in which tertiary interactions do not define RNA 3D structure, but rather, help select specific conformers from an already narrow, topologically pre-defined conformational distribution. Studies are providing fundamental insights into the nature of these topological constraints, how they are encoded by the RNA secondary structure, and how they interplay with other interactions, breathing new meaning to RNA secondary struct... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4751849 Wed, 13 Apr 2011 23:00:00 +0100 4751849 http://www.medworm.com/index.php?rid=4751835&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21497504%26dopt%3DAbstract Authors: Wass MN, David A, Sternberg MJ Macromolecular interactions are central to most cellular processes. Experimental methods generate diverse data on these interactions ranging from high throughput protein-protein interactions (PPIs) to the crystallised structures of complexes. Despite this, only a fraction of interactions have been identified and therefore predictive methods are essential to fill in the numerous gaps. Many predictive methods use information from related proteins. Accordingly, we review the conservation of interface and ligand binding sites within protein families and their association with conserved residues and Specificity Determining Positions. We then review recent developments in predictive methods for the identification of PPIs, protein interface sites and sm... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4751835 Wed, 13 Apr 2011 23:00:00 +0100 4751835 http://www.medworm.com/index.php?rid=4751848&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21497084%26dopt%3DAbstract Authors: Godzik A Metagenomics sequencing projects have dramatically increased our knowledge of the protein universe and provided over one-half of currently known protein sequences; they have also introduced a much broader phylogenetic diversity into the protein databases. The full analysis of metagenomic datasets is only beginning, but it has already led to the discovery of thousands of new protein families, likely representing novel functions specific to given environments. At the same time, a deeper analysis of such novel families, including experimental structure determination of some representatives, suggests that most of them represent distant homologs of already characterized protein families, and thus most of the protein diversity present in the new environments are due to func... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4751848 Tue, 12 Apr 2011 23:00:00 +0100 4751848 http://www.medworm.com/index.php?rid=4751869&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21482100%26dopt%3DAbstract Authors: Olson WK, Zhurkin VB Condensation of DNA in the nucleosome takes advantage of its double-helical architecture. The DNA deforms at sites where the base pairs face the histone octamer. The largest so-called kink-and-slide deformations occur in the vicinity of arginines that penetrate the minor groove. Nucleosome structures formed from the 601 positioning sequence differ subtly from those incorporating an AT-rich human α-satellite DNA. Restraints imposed by the histone arginines on the displacement of base pairs can modulate the sequence-dependent deformability of DNA and potentially contribute to the unique features of the different nucleosomes. Steric barriers mimicking constraints found in the nucleosome induce the simulated large-scale rearrangement of canonical B DNA to kin... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4751869 Wed, 06 Apr 2011 23:00:00 +0100 4751869 http://www.medworm.com/index.php?rid=4751862&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21482101%26dopt%3DAbstract Authors: Brown CJ, Johnson AK, Dunker AK, Daughdrill GW The evolution of disordered proteins or regions of proteins differs from that of ordered proteins because of the differences in their sequence composition, intramolecular contacts, and function. Recent assessments of disordered protein evolution at the sequence, structural, and functional levels support this hypothesis. Disordered proteins have a different pattern of accepted point mutations, exhibit higher rates of insertions and deletions, and generally, but not always, evolve more rapidly than ordered proteins. Even with these high rates of sequence evolution, a few examples have shown that disordered proteins maintain their flexibility under physiological conditions, and it is hypothesized that they maintain specific structura... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4751862 Wed, 06 Apr 2011 23:00:00 +0100 4751862 http://www.medworm.com/index.php?rid=4751855&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21482102%26dopt%3DAbstract Authors: Zahn KE, Wallace SS, Doublié S Deducing the structure of the DNA double helix in 1953 implied the mode of its replication: Watson-Crick (WC) base pairing might instruct an enzyme, now known as the DNA polymerase, during the synthesis of a daughter stand complementary to a single strand of the parental double helix. What has become increasingly clear in the last 60 years, however, is that adducted and oxidatively generated DNA bases are ubiquitous in physiological DNA, and all organisms conserve multiple DNA polymerases specialized for DNA synthesis opposite these damaged templates. Here, we review recent crystal structures depicting replicative and bypass DNA polymerases encountering two typical lesions arising from the oxidation of DNA: abasic sites, which block the replicat... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4751855 Wed, 06 Apr 2011 23:00:00 +0100 4751855 http://www.medworm.com/index.php?rid=4751870&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21474301%26dopt%3DAbstract Authors: Reiter NJ, Chan CW, Mondragón A Extensive networks of tertiary interactions give rise to unique, highly organized domain architectures that characterize the three-dimensional structure of large RNA molecules. Formed by stacked layers of a near-planar arrangement of contiguous coaxial helices, large RNA molecules are relatively flat in overall shape. The functional core of these molecules is stabilized by a diverse set of tertiary interaction motifs that often bring together distant regions of conserved nucleotides. Although homologous RNAs from different organisms can be structurally diverse, they adopt a structurally conserved functional core that includes preassembled active and/or substrate binding sites. These findings broaden our understanding of RNA folding and tertiary... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4751870 Mon, 04 Apr 2011 23:00:00 +0100 4751870 http://www.medworm.com/index.php?rid=4751872&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21458982%26dopt%3DAbstract Authors: Söding J, Remmert M Protein sequence comparison methods have grown increasingly sensitive during the last decade and can often identify distantly related proteins sharing a common ancestor some 3 billion years ago. Although cellular function is not conserved so long, molecular functions and structures of protein domains often are. In combination with a domain-centered approach to function and structure prediction, modern remote homology detection methods have a great and largely underexploited potential for elucidating protein functions and evolution. Advances during the last few years include nonlinear scoring functions combining various sequence features, the use of sequence context information, and powerful new software packages. Since progress depends on realistically ass... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4751872 Wed, 30 Mar 2011 23:00:00 +0100 4751872 http://www.medworm.com/index.php?rid=4751871&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21458983%26dopt%3DAbstract Authors: Meng EC, Babbitt PC In functionally diverse enzyme superfamilies (SFs), conserved structural and active site features reflect catalytic capabilities 'hard-wired' in each SF architecture. Overlaid on this foundation, evolutionary changes in active site machinery, structural topology and other aspects of structural organization and interactions support the emergence of new reactions, mechanisms, and substrate specificity. This review connects topological with functional variation in each of the haloalkanoic acid dehalogenase (HAD) and vicinal oxygen chelate fold (VOC) SFs and a set of redox-active thioredoxin (Trx)-fold SFs to illustrate a few of the varied themes nature has used to evolve new functions from a limited set of structural scaffolds. PMID: 21458983 [PubMed - as ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4751871 Wed, 30 Mar 2011 23:00:00 +0100 4751871 http://www.medworm.com/index.php?rid=4751874&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21439812%26dopt%3DAbstract Authors: Montaño SP, Rice PA Mobile DNA elements are found in all kingdoms of life, and they employ numerous mechanisms to move within and between genomes. Here we review recent structural advances in understanding two very different families of DNA transposases and retroviral integrases: the DDE and Y1 groups. Even within the DDE family which shares a conserved catalytic domain, there is great diversity in the architecture of the synaptic complexes formed by the intact enzymes with their cognate element-end DNAs. However, recurring themes arise from comparing these complexes, such as stabilization by an intertwined network of protein-DNA and protein-protein contacts, and catalysis in trans, where each active subunit catalyzes the chemical steps on one DNA segment but also binds speci... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4751874 Wed, 23 Mar 2011 00:00:00 +0100 4751874 http://www.medworm.com/index.php?rid=4751873&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21439813%26dopt%3DAbstract Authors: Parker SC, Tullius TD Although the three-letter genetic code that maps nucleotide sequence to protein sequence is well known, there must exist other codes that are embedded in the human genome. Recent work points to sequence-dependent variation in DNA shape as one mechanism by which regulatory and other information could be encoded in DNA. Recent advances include the discovery of shape-dependent recognition of DNA that depends on minor groove width and electrostatics, the existence of overlapping codes in protein-coding regions of the genome, and evolutionary selection for compensatory changes in nucleotide composition that facilitate nucleosome occupancy. It is becoming clear that DNA shape is important to biological function, and therefore will be subject to evolutionary con... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4751873 Wed, 23 Mar 2011 00:00:00 +0100 4751873 http://www.medworm.com/index.php?rid=4638033&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21419622%26dopt%3DAbstract Authors: Rey FA, Sundquist WI PMID: 21419622 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4638033 Wed, 16 Mar 2011 00:00:00 +0100 4638033 http://www.medworm.com/index.php?rid=4638034&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21414772%26dopt%3DAbstract Authors: Skolnick J, Friesner R PMID: 21414772 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4638034 Tue, 15 Mar 2011 00:00:00 +0100 4638034 http://www.medworm.com/index.php?rid=4578743&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21377352%26dopt%3DAbstract Authors: Glatt S, Alfieri C, Müller CW The X-ray structure of the nucleosome core particle (NCP) has been a major milestone in the structural biology of chromatin. Since, our understanding how NCPs interact with multiple partners has been extending from single chromatin-binding domains recognizing post-translational modifications (PTMs) in histone tails towards the recognition of higher-order chromatin structure by multi-subunit chromatin remodeling complexes. The current review summarizes recent progress in the structural biology of nucleosome-recognition from chromatin-binding domains to multi-protein remodeling complexes. PMID: 21377352 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4578743 Thu, 03 Mar 2011 00:00:00 +0100 4578743 http://www.medworm.com/index.php?rid=4578744&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21371882%26dopt%3DAbstract Authors: Wu C, Shea JE The aggregation of soluble proteins into fibrillar species is a complex process that spans many lengths and time scales, and that involves the formation of numerous on-pathway and off-pathway intermediate species. Despite this complexity, several elements underlying the aggregation process appear to be universal. The kinetics typically follows a nucleation-growth process, and proteins with very different sequences aggregate to form similar fibril structures, populating intermediates with sufficient structural similarity to bind to a common antibody. This review focuses on a computational approach that exploits the common features of aggregation to simplify or 'coarse-grain' the representation of the protein. We highlight recent developments in coarse-grained mode... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4578744 Tue, 01 Mar 2011 00:00:00 +0100 4578744 http://www.medworm.com/index.php?rid=4578745&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21353529%26dopt%3DAbstract Authors: Erdin S, Lisewski AM, Lichtarge O Genomic centers discover increasingly many protein sequences and structures, but not necessarily their full biological functions. Thus, currently, less than one percent of proteins have experimentally verified biochemical activities. To fill this gap, function prediction algorithms apply metrics of similarity between proteins on the premise that those sufficiently alike in sequence, or structure, will perform identical functions. Although high sensitivity is elusive, network analyses that integrate these metrics together hold the promise of rapid gains in function prediction specificity. PMID: 21353529 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4578745 Thu, 24 Feb 2011 00:00:00 +0100 4578745 http://www.medworm.com/index.php?rid=4525296&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21349700%26dopt%3DAbstract Authors: Chodera JD, Mobley DL, Shirts MR, Dixon RW, Branson K, Pande VS Improved rational drug design methods are needed to lower the cost and increase the success rate of drug discovery and development. Alchemical binding free energy calculations, one potential tool for rational design, have progressed rapidly over the past decade, but still fall short of providing robust tools for pharmaceutical engineering. Recent studies, especially on model receptor systems, have clarified many of the challenges that must be overcome for robust predictions of binding affinity to be useful in rational design. In this review, inspired by a recent joint academic/industry meeting organized by the authors, we discuss these challenges and suggest a number of promising approaches for overcoming them. ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4525296 Tue, 22 Feb 2011 00:00:00 +0100 4525296 http://www.medworm.com/index.php?rid=4525297&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21339062%26dopt%3DAbstract Authors: Gallicchio E, Levy RM Conformational dynamics plays a fundamental role in the regulation of molecular recognition processes. Conformational heterogeneity and entropy variations upon binding, although not always evident from the analysis of structural data, can substantially affect affinity and specificity. Computer modeling is able to provide some of the most direct insights into these aspects of molecular recognition. We review recent physics-based computational studies that employ advanced conformational sampling algorithms and effective potentials to model the three main classes of degrees of freedom relevant to the binding process: ligand positioning relative to the receptor, ligand and receptor internal reorganization, and hydration. Collectively these studies show that a... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4525297 Sat, 19 Feb 2011 00:00:00 +0100 4525297 http://www.medworm.com/index.php?rid=4525300&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21333526%26dopt%3DAbstract Authors: Grigorieff N, Harrison SC Nine different near-atomic resolution structures of icosahedral viruses, determined by electron cryo-microscopy and published between early 2008 and late 2010, fulfil predictions made 15 years ago that single-particle cryo-EM techniques could visualize molecular detail at 3-4Å resolution. This review summarizes technical developments, both in instrumentation and in computation, that have led to the new structures, which advance our understanding of virus assembly and cell entry. PMID: 21333526 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4525300 Wed, 16 Feb 2011 00:00:00 +0100 4525300 http://www.medworm.com/index.php?rid=4525299&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21333527%26dopt%3DAbstract Authors: Elber R Allosteric transitions are one of the subtler mechanisms used by nature to fine tune protein activity. Effector binding to a specific site on the protein surface induces significant activity change, and initiates a conformational transition that frequently includes domain motions and is very large. From a theoretical and biophysical perspective two problems are particularly intriguing. The first is the way in which a launching signal, which is spatially confined and includes only a few interacting atoms, is propagated to a large-scale conformational transition we frequently see in allosteric transitions. Hence, there is the question of how a small perturbation is magnified to yield motions of thousands of atoms. The second puzzle is of focus, coherence, and efficiency.... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4525299 Wed, 16 Feb 2011 00:00:00 +0100 4525299 http://www.medworm.com/index.php?rid=4525298&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21333528%26dopt%3DAbstract Authors: Faraldo-Gómez JD, Forrest LR The molecular mechanisms of membrane proteins that are activated either by ions or by ATP are just beginning to come into focus, as long-awaited structural data are revealed. This information is being leveraged and supplemented to great effect by molecular modeling and computer simulation studies. Important examples include the homology modeling of eukaryotic protein structures based on distantly related templates, as well as the use of internal structural symmetry for modeling different states in conformational cycles. Molecular simulation studies have elucidated the location and coordination structure of ion binding sites, and explained their selectivity, while also providing tantalizing insights into the mechanisms that couple conformational ch... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4525298 Wed, 16 Feb 2011 00:00:00 +0100 4525298 http://www.medworm.com/index.php?rid=4525301&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21330133%26dopt%3DAbstract Authors: Schulz EC, Ficner R Hallmarks of proteins that contain β-helices are their increased stability and rigidity and their aggregation prone folding pathways. While parallel β-helices fold independently, the folding and assembly of many triple β-helices depends on a registration signal in order to adopt the correct three-dimensional structure. In some cases this is a mere trimerization domain, in others specialized chaperones are required. Recently, the crystal structures of two classes of intramolecular chaperones of β-helical proteins have been determined. Both mediate the assembly of large tailspike proteins and release themselves after maturation; however, they differ substantially in their structure and autoproteolytic release mechanisms. PMID: 21330133 [PubMed - as su... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4525301 Tue, 15 Feb 2011 00:00:00 +0100 4525301 http://www.medworm.com/index.php?rid=4525302&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21320770%26dopt%3DAbstract Authors: Stein A, Mosca R, Aloy P High-throughput interaction discovery initiatives have revealed the existence of hundreds of multiprotein complexes whose functions are regulated through thousands of protein-protein interactions (PPIs). However, the structural details of these interactions, often necessary to understand their function, are only available for a tiny fraction, and the experimental difficulties surrounding complex structure determination make computational modeling techniques paramount. In this manuscript, we critically review some of the most recent developments in the field of structural bioinformatics applied to the modeling of protein interactions and complexes, from large macromolecular machines to domain-domain and peptide-mediated interactions. In particular, we p... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4525302 Sat, 12 Feb 2011 00:00:00 +0100 4525302 http://www.medworm.com/index.php?rid=4525303&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21316217%26dopt%3DAbstract Authors: Wilson DN, Beckmann R As the nascent polypeptide chain is being synthesized, it passes through a tunnel within the large ribosomal subunit and emerges at the solvent side where protein folding occurs. Despite the universality and conservation of dimensions of the ribosomal tunnel, a functional role for the ribosomal tunnel is only beginning to emerge: Rather than a passive conduit for the nascent chain, accumulating evidence indicates that the tunnel plays a more active role. In this article, we discuss recent structural insights into the role of the tunnel environment, and its implications for protein folding, co-translational targeting and translation regulation. PMID: 21316217 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4525303 Thu, 10 Feb 2011 00:00:00 +0100 4525303 http://www.medworm.com/index.php?rid=4525304&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21315581%26dopt%3DAbstract Authors: Yeates TO, Thompson MC, Bobik TA Details are emerging on the structure and function of a remarkable class of capsid-like protein assemblies that serve as simple metabolic organelles in many bacteria. These bacterial microcompartments consist of a few thousand shell proteins, which encapsulate two or more sequentially acting enzymes in order to enhance or sequester certain metabolic pathways, particularly those involving toxic or volatile intermediates. Genomic data indicate that bacterial microcompartment shell proteins are present in a wide range of bacterial species, where they encapsulate varied reactions. Crystal structures of numerous shell proteins from distinct types of microcompartments have provided keys for understanding how the shells are assembled and how they cond... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4525304 Wed, 09 Feb 2011 00:00:00 +0100 4525304 http://www.medworm.com/index.php?rid=4470682&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21296569%26dopt%3DAbstract We present a critical review of these structural models, illustrating the strengths and challenges of the integrative approach. PMID: 21296569 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4470682 Fri, 04 Feb 2011 00:00:00 +0100 4470682 http://www.medworm.com/index.php?rid=4470683&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21292475%26dopt%3DAbstract Authors: Xie L, Xie L, Bourne PE Here off-target binding implies the binding of a small molecule of therapeutic interest to a protein target other than the primary target for which it was intended. Increasingly such off-targeting appears to be the norm rather than the exception, rational drug design notwithstanding, and can lead to detrimental side-effects, or opportunities to reposition a therapeutic agent to treat a different condition. Not surprisingly, there is significant interest in determining a priori what off-targets exist on a proteome-wide scale. Beyond determining putative off-targets is the need to understand the impact of such binding on the complete biological system, with the ultimate goal of being able to predict the phenotypic outcome. While a very ambitious goal, som... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4470683 Tue, 01 Feb 2011 00:00:00 +0100 4470683 http://www.medworm.com/index.php?rid=4470684&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21288713%26dopt%3DAbstract Authors: Duda DM, Scott DC, Calabrese MF, Zimmerman ES, Zheng N, Schulman BA Cullin-RING ligases (CRLs) compose the largest class of E3 ubiquitin ligases. CRLs are modular, multisubunit enzymes, comprising interchangeable substrate receptors dedicated to particular Cullin-RING catalytic cores. Recent structural studies have revealed numerous ways in which CRL E3 ligase activities are controlled, including multimodal E3 ligase activation by covalent attachment of the ubiquitin-like protein NEDD8, inhibition of CRL assembly/activity by CAND1, and several mechanisms of regulated substrate recruitment. These features highlight the potential for CRL activities to be tuned in responses to diverse cellular cues, and for modulating CRL functions through small-molecule agonists or antagonists. ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4470684 Mon, 31 Jan 2011 00:00:00 +0100 4470684 http://www.medworm.com/index.php?rid=4470685&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21282052%26dopt%3DAbstract Authors: Lyubimov AY, Strycharska M, Berger JM Ring-shaped, oligomeric translocases are multisubunit enzymes that couple the hydrolysis of Nucleoside TriPhosphates (NTPs) to directed movement along extended biopolymer substrates. These motors help unwind nucleic acid duplexes, unfold protein chains, and shepherd nucleic acids between cellular and/or viral compartments. Substrates are translocated through a central pore formed by a circular array of catalytic subunits. Cycles of nucleotide binding, hydrolysis, and product release help reposition translocation loops in the pore to direct movement. How NTP turnover allosterically induces these conformational changes, and the extent of mechanistic divergence between motor families, remain outstanding problems. This review examines the curr... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4470685 Sat, 29 Jan 2011 00:00:00 +0100 4470685 http://www.medworm.com/index.php?rid=4470686&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21277766%26dopt%3DAbstract Authors: Cherepanov P, Maertens GN, Hare S Retroviral replication depends on successful integration of the viral genetic material into a host cell chromosome. Virally encoded integrase, an enzyme from the DDE(D) nucleotidyltransferase superfamily, is responsible for the key DNA cutting and joining steps associated with this process. Insights into the structural and mechanistic aspects of integration are directly relevant for the development of antiretroviral drugs. Recent breakthroughs have led to biochemical and structural characterization of the principal integration intermediates revealing the tetramer of integrase that catalyzes insertion of both 3' viral DNA ends into a sharply bent target DNA. This review discusses the mechanism of retroviral DNA integration and the mode of actio... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4470686 Fri, 28 Jan 2011 00:00:00 +0100 4470686 http://www.medworm.com/index.php?rid=4400226&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21256733%26dopt%3DAbstract Authors: Petrov A, Kornberg G, O'Leary S, Tsai A, Uemura S, Puglisi JD The recent growth in single molecule studies of translation has provided an insight into the molecular mechanism of ribosomal function. Single molecule fluorescence approaches allowed direct observation of the structural rearrangements occurring during translation and revealed dynamic motions of the ribosome and its ligands. These studies demonstrated how ligand binding affects dynamics of the ribosome, and the role of the conformational sampling in large-scale rearrangements intrinsic to translation elongation. The application of time-resolved cryo-electron microscopy revealed new conformational intermediates during back-translocation providing an insight into ribosomal dynamics from an alternative perspective. Rec... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4400226 Thu, 20 Jan 2011 00:00:00 +0100 4400226 http://www.medworm.com/index.php?rid=4400227&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21247754%26dopt%3DAbstract Authors: Wang J, Qiu JX, Soto C, Degrado WF The M2 proton channel from influenza A virus, a prototype for a class of viral ion channels known as viroporins, conducts protons along a chain of water molecules and ionizable sidechains, including His37. Recent studies highlight a delicate interplay between protein folding, proton binding, and proton conduction through the channel. Drugs inhibit proton conduction by binding to an aqueous cavity adjacent to M2's proton-selective filter, thereby blocking access of proton to the filter, and altering the energetic landscape of the channel and the energetics of proton-binding to His37. PMID: 21247754 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4400227 Mon, 17 Jan 2011 00:00:00 +0100 4400227 http://www.medworm.com/index.php?rid=4400228&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21227680%26dopt%3DAbstract Authors: Tan S, Nagai K PMID: 21227680 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4400228 Mon, 10 Jan 2011 00:00:00 +0100 4400228 http://www.medworm.com/index.php?rid=4335584&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21196111%26dopt%3DAbstract Authors: Gilson MK, Radford SE PMID: 21196111 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4335584 Fri, 31 Dec 2010 00:00:00 +0100 4335584 http://www.medworm.com/index.php?rid=4335585&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21185718%26dopt%3DAbstract Authors: Yin YW DNA polymerase gamma (Pol γ) is a nuclear encoded, mitochondrially located replicase that conducts all DNA synthesis in the organelle. Structurally, human Pol γ closely resembles bacteriophage T7 DNA polymerase. Perhaps due to this prokaryotic-like feature, Pol γ is highly susceptible to inhibition by drugs designed against HIV reverse transcriptase and HCV RNA polymerase. In this review, I summarize recent structural and biochemical studies towards understanding Pol γ-mediated antiviral drug toxicity. PMID: 21185718 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4335585 Thu, 23 Dec 2010 00:00:00 +0100 4335585 http://www.medworm.com/index.php?rid=4335586&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21176878%26dopt%3DAbstract Authors: Tan S, Davey CA Chromatin plays a fundamental role in eukaryotic genomic regulation, and the increasing awareness of the importance of epigenetic processes in human health and disease emphasizes the need for understanding the structure and function of the nucleosome. Recent advances in chromatin structural studies, including the first structures of nucleosomes containing the Widom 601 sequence and the structure of a chromatin protein-nucleosome assembly, have provided new insight into stretching of nucleosomal DNA, nucleosome positioning, binding of metal ions, drugs and therapeutic candidates to nucleosomes, and nucleosome recognition by nuclear proteins. These discoveries ensure promising future prospects for unravelling structural attributes of chromatin. PMID: 21176878... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4335586 Sun, 19 Dec 2010 00:00:00 +0100 4335586 http://www.medworm.com/index.php?rid=4276156&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21168327%26dopt%3DAbstract Authors: Mason M, Schuller A, Skordalakes E Telomeres and their associated proteins are specialized structures at the ends of linear chromosomes that function as caps that protect the DNA from exonuclease degradation and recombination events that could lead to genomic instability. In this review, we discuss recent publications describing the high-resolution structures of individual domains and of the full-length catalytic subunit of telomerase alone and in complex with its putative RNA template and telomeric DNA. These structures, together with existing biochemical data, provide novel insights into the basic mechanism of telomere replication and length homeostasis by telomerase. Moreover, these data further enrich our understanding of the mechanism of DNA replication by polymerases in ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4276156 Thu, 16 Dec 2010 00:00:00 +0100 4276156 http://www.medworm.com/index.php?rid=4276158&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21145228%26dopt%3DAbstract We present effects of recently characterized viral and cellular RNAs on regulation of PKR, as well as siRNAs. A central conclusion is that assembly of accessible long double-stranded RNA (dsRNA) elements within biological RNAs plays a key role in regulation of PKR kinase. Strategies for forming such elements include RNA dimerization, formation of symmetrical helical defects, A-form dsRNA mimicry, and coaxial stacking of helices. PMID: 21145228 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4276158 Tue, 07 Dec 2010 00:00:00 +0100 4276158 http://www.medworm.com/index.php?rid=4276157&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21145229%26dopt%3DAbstract Authors: Lee SJ, Jiko C, Yamashita E, Tsukihara T The timely nuclear-cytoplasmic translocation of proteins and RNAs by importins and exportins is important for controlling biological processes. Since the 2004 publication of the first exportin structure, Cse1p, the X-ray structures of exportin-5 complexed with pre-microRNA, exportin-t complexed with tRNA, and three CRM1-related structures have revealed the binding mechanism involved in specific cargo recognition. Pre-microRNA and tRNA have conserved 3' 2-4-nucleotide overhang motifs and similar short double-stranded regions. Exportin-5 and exportin-t bind a conserved 3' overhang strongly, and they weakly enclose the short double-stranded stems, each in a different manner. The structures of the nuclear export complexes of small double-st... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4276157 Tue, 07 Dec 2010 00:00:00 +0100 4276157 http://www.medworm.com/index.php?rid=4276159&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21144739%26dopt%3DAbstract Authors: Sosnick TR, Barrick D Rather than stressing the most recent advances in the field, this review highlights the fundamental topics where disagreement remains and where adequate experimental data are lacking. These topics include properties of the denatured state and the role of residual structure, the nature of the fundamental steps and barriers, the extent of pathway heterogeneity and non-native interactions, recent comparisons between theory and experiment, and finally, dynamical properties of the folding reaction. PMID: 21144739 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4276159 Mon, 06 Dec 2010 00:00:00 +0100 4276159 http://www.medworm.com/index.php?rid=4217964&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21094598%26dopt%3DAbstract Authors: Dessen A, Xu W PMID: 21094598 [PubMed - in process] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4217964 Wed, 01 Dec 2010 00:00:00 +0100 4217964 http://www.medworm.com/index.php?rid=4217961&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21112769%26dopt%3DAbstract Authors: Gershenson A, Gierasch LM It is hard to imagine a more extreme contrast than that between the dilute solutions used for in vitro studies of protein folding and the crowded, compartmentalized, sticky, spatially inhomogeneous interior of a cell. This review highlights recent research exploring protein folding in the cell with a focus on issues that are generally not relevant to in vitro studies of protein folding, such as macromolecular crowding, hindered diffusion, cotranslational folding, molecular chaperones, and evolutionary pressures. The technical obstacles that must be overcome to characterize protein folding in the cell are driving methodological advances, and we draw attention to several examples, such as fluorescence imaging of folding in cells and genetic screens for ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4217961 Fri, 26 Nov 2010 00:00:00 +0100 4217961 http://www.medworm.com/index.php?rid=4217962&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21111607%26dopt%3DAbstract Authors: Zhang G, Ignatova Z In the living cells, the folding of many proteins is largely believed to begin co-translationally, during their biosynthesis at the ribosomes. In the ribosomal tunnel, the nascent peptide may establish local interactions and stabilize α-helical structures. Long-range contacts are more likely outside the ribosomes after release of larger segments of the nascent chain. Examples suggest that domains can attain native-like structure on the ribosome with and without population of folding intermediates. The co-translational folding is limited by the speed of the gradual extrusion of the nascent peptide which imposes conformational restraints on its folding landscape. Recent experimental and in silico modeling studies indicate that translation kinetics fine-tunes... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4217962 Wed, 24 Nov 2010 00:00:00 +0100 4217962 http://www.medworm.com/index.php?rid=4217963&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21109422%26dopt%3DAbstract Authors: Tzeng SR, Kalodimos CG Allostery, the process by which distant sites within a protein system are energetically coupled, is an efficient and ubiquitous mechanism for activity regulation. A purely mechanical view of allostery invoking only structural changes has developed over the decades as the classical view of the phenomenon. However, a fast growing list of examples illustrate the intimate link between internal motions over a wide range of time scales and function in protein-ligand interactions. Proteins respond to perturbations by redistributing their motions and they use fluctuating conformational states for binding and conformational entropy as a carrier of allosteric energy to modulate association with ligands. In several cases allosteric interactions proceed with minimal... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4217963 Tue, 23 Nov 2010 00:00:00 +0100 4217963 http://www.medworm.com/index.php?rid=4184965&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21081274%26dopt%3DAbstract Authors: Bowman GR, Voelz VA, Pande VS Protein folding is an important problem in structural biology with significant medical implications, particularly for misfolding disorders like Alzheimer's disease. Solving the folding problem will ultimately require a combination of theory and experiment, with theoretical models providing a comprehensive view of folding and experiments grounding these models in reality. Here we review progress towards this goal over the past decade, with an emphasis on recent theoretical advances that are empowering chemically detailed models of folding and the new results these technologies are providing. In particular, we discuss new insights made possible by Markov state models (MSMs), including the role of non-native contacts and the hub-like character of pro... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4184965 Sun, 14 Nov 2010 00:00:00 +0100 4184965 http://www.medworm.com/index.php?rid=4184966&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21075614%26dopt%3DAbstract Authors: Bowie JU Water is an inhospitable environment for protein hydrogen bonds because it is polarizable and capable of forming competitive hydrogen bonds. In contrast, the apolar core of a biological membrane seems like an ideal environment for hydrogen bonds, and it has long been assumed that hydrogen bonding should be a powerful force driving membrane protein folding. Nevertheless, while backbone hydrogen bonds may be much stronger in membrane proteins, experimental measurements indicate that side chain hydrogen bond strengths are not strikingly different in membrane and water soluble proteins. How is this possible? I argue that model compounds in apolar solvents do not adequately describe the system because the protein itself is ignored. The protein chain provides a rich source ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4184966 Fri, 12 Nov 2010 00:00:00 +0100 4184966 http://www.medworm.com/index.php?rid=4184967&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21074407%26dopt%3DAbstract Authors: Zeqiraj E, van Aalten DM Protein kinases provide a platform for the integration of signal transduction networks. A key feature of transmitting these cellular signals is the ability of protein kinases to activate one another by phosphorylation. A number of kinases are predicted by sequence homology to be incapable of phosphoryl group transfer due to degradation of their catalytic motifs. These are termed pseudokinases and because of the assumed lack of phosphoryltransfer activity their biological role in cellular transduction has been mysterious. Recent structure-function studies have uncovered the molecular determinants for protein kinase inactivity and have shed light to the biological functions and evolution of this enigmatic subset of the human kinome. Pseudokinases act as ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4184967 Wed, 10 Nov 2010 00:00:00 +0100 4184967 http://www.medworm.com/index.php?rid=4166072&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21071205%26dopt%3DAbstract Authors: Schreiber G, Keating AE Interactions between macromolecules in general, and between proteins in particular, are essential for any life process. Examples include transfer of information, inhibition or activation of function, molecular recognition as in the immune system, assembly of macromolecular structures and molecular machines, and more. Proteins interact with affinities ranging from millimolar to femtomolar and, because affinity determines the concentration required to obtain 50% binding, the amount of different complexes formed is very much related to local concentrations. Although the concentration of a specific binding partner is usually quite low in the cell (nanomolar to micromolar), the total concentration of other macromolecules is very high, allowing weak and non-s... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4166072 Tue, 09 Nov 2010 00:00:00 +0100 4166072 http://www.medworm.com/index.php?rid=4166071&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21071206%26dopt%3DAbstract Authors: Marletta MA, Fontecave M PMID: 21071206 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4166071 Tue, 09 Nov 2010 00:00:00 +0100 4166071 http://www.medworm.com/index.php?rid=4123182&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21030247%26dopt%3DAbstract Authors: Matteï PJ, Neves D, Dessen A The bacterial cell wall is a complex three-dimensional structure that protects the cell from environmental stress and ensures its shape. The biosynthesis of its main component, the peptidoglycan, involves the coordination of activities of proteins present in the cytoplasm, the membrane, and the periplasm, some of which also interact with the bacterial cytoskeleton. The sheer complexity of the cell wall elongation process, which is the main focus of this review, has created a significant challenge for the study of the macromolecular interactions that regulate peptidoglycan biosynthesis. The availability of new structural and biochemical data on a number of components of peptidoglycan assembly machineries, including a complex between MreB and RodZ a... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4123182 Tue, 26 Oct 2010 00:00:00 +0100 4123182 http://www.medworm.com/index.php?rid=4107874&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20970991%26dopt%3DAbstract Authors: Hou H, Yu H Posttranslational modifications of histone tails are crucial epigenetic marks that regulate diverse cellular processes. Histone lysine methylation activates or represses transcription, depending on the site and degree of these modifications. Two classes of histone lysine demethylases remove histone methylation. Lysine demethylase 1 (KDM1, also known as LSD1) is a flavin adenine dinucleotide (FAD)-containing enzyme that removes mono-/di-methylation. The Jumonji C-terminal domain (JmjC) family of histone demethylases uses Fe(2+) and α-ketoglutarate as cofactors to remove all methylation states. Structural studies have provided insights into the overall architecture, the catalytic mechanism, and the substrate specificity of histone demethylases. Here, we review these... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4107874 Wed, 20 Oct 2010 23:00:00 +0100 4107874 http://www.medworm.com/index.php?rid=4107873&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20970992%26dopt%3DAbstract Authors: Low HH, Löwe J Dynamins form a family of eukaryotic and prokaryotic proteins involved in membrane fission, fusion and restructuring. They have complex mechanisms of self-assembly, which are coupled to the tubulation and destabilization of lipid bilayers. Recent structural data has revolutionized our understanding and is now yielding detailed insights into dynamin structure, from monomer through to polymer. Traditional division of the dynamin subunit into GTPase domain, middle domain and GTPase effector domain based on sequence alignments and biochemistry is not supported by recent structural data. A unified model of dynamin architecture is presented here, based on observation that the basic dynamin fold is conserved across evolutionary kingdoms. PMID: 20970992 [PubMed - a... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4107873 Wed, 20 Oct 2010 23:00:00 +0100 4107873 http://www.medworm.com/index.php?rid=4107872&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20970993%26dopt%3DAbstract Authors: Boraston A, Mulloy B PMID: 20970993 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4107872 Wed, 20 Oct 2010 23:00:00 +0100 4107872 http://www.medworm.com/index.php?rid=4088266&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20956082%26dopt%3DAbstract Authors: Justin N, De Marco V, Aasland R, Gamblin SJ The phenotypes of different cell types are governed by their differential gene expression programmes, which are prominently influenced by epigenetic gene regulation featuring heritable chromatin states. Different epigenetic states are associated with distinctive patterns of post-translational modifications of the histone tails, which in turn influence the recruitment of chromatin-modifying effectors and local chromatin structure. Despite rapid advances in understanding how particular histone marks correlate with transcriptional output, many of the molecular details on how the maintenance and alteration of these modifications relate to fundamental processes such as replication, DNA repair, and transcription remain to be elucidated. He... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4088266 Fri, 15 Oct 2010 23:00:00 +0100 4088266 http://www.medworm.com/index.php?rid=4088269&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20951571%26dopt%3DAbstract Authors: Atta M, Mulliez E, Arragain S, Forouhar F, Hunt JF, Fontecave M Proteins and RNA molecules enjoy a variety of chemically complex post-translational and post-transcriptional modifications. The chemistry at work in these reactions, which was considered to be exclusively ionic in nature has recently been shown to depend on radical mechanisms in some cases. The overwhelming majority of these radical-based reactions are catalyzed by 'Radical-SAM' enzymes. This review article highlights mechanistic and structural aspects of this class of reactions and indicates important research directions to be addressed. PMID: 20951571 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4088269 Wed, 13 Oct 2010 23:00:00 +0100 4088269 http://www.medworm.com/index.php?rid=4088268&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20951572%26dopt%3DAbstract Authors: van der Donk WA, Krebs C, Bollinger JM A growing number of non-heme-iron oxygenases and oxidases catalyze reactions for which the well-established mechanistic paradigm involving a single C-H-bond-cleaving intermediate of the Fe(IV)-oxo (ferryl) type [1(•)] is insufficient to explain the chemistry. It is becoming clear that, in several of these cases, Fe(III)-superoxide complexes formed by simple addition of O(2) to the reduced [Fe(II)] cofactor initiate substrate oxidation by abstracting hydrogen [2,3(•)]. This substrate-oxidizing entry route into high-valent-iron intermediates makes possible an array of complex and elegant oxidation reactions without the consumption of valuable reducing equivalents. Examples of this novel mechanistic strategy are discussed with the goal o... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4088268 Wed, 13 Oct 2010 23:00:00 +0100 4088268 http://www.medworm.com/index.php?rid=4088267&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20951573%26dopt%3DAbstract Authors: Melcher K, Zhou XE, Xu HE Abscisic acid (ABA) is a plant hormone with important functions in stress protection and physiology. Recently, the PYR/PYL/RCAR family of intracellular ABA receptors was identified. These receptors directly link ABA perception to a canonical ABA signaling pathway, in which ABA-bound receptors bind and inhibit type 2C phosphatases. High resolution crystal structures of members of this family have been solved in all relevant states: as apo receptors, bound to ABA, and as receptor-ABA-phosphatase complexes. Together, these structures provide a detailed gate-latch-lock mechanism of ABA recognition, receptor-PP2C interaction, and inhibition of the PP2C phosphatase activity and provide a basis for the design of synthetic ABA agonists for stress protection o... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4088267 Wed, 13 Oct 2010 23:00:00 +0100 4088267 http://www.medworm.com/index.php?rid=4088272&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20951026%26dopt%3DAbstract Authors: Xu D, Farmer A, Chook YM The Karyopherin-β family of nuclear transport factors mediates the majority of nucleocytoplasmic transport. Although each of the 19 Karyopherin-βs transports unique sets of cargos, only three classes of nuclear localization and export signals, or NLSs and NESs, have been characterized. The short basic classical-NLS was first discovered in the 1980s and their karyopherin-bound structures were first reported more than 10 years ago. More recently, structural and biophysical studies of Karyopherin-β2-cargo complexes led to definition of the complex and diverse PY-NLS. Structural knowledge of the leucine-rich NES is finally available more than 10 years after the discovery of its recognition by the exportin CRM1. We review recent findings relating to how ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4088272 Tue, 12 Oct 2010 23:00:00 +0100 4088272 http://www.medworm.com/index.php?rid=4088271&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20951027%26dopt%3DAbstract Authors: Casino P, Rubio V, Marina A Two-component systems, composed of a homodimeric histidine kinase (HK) and a response regulator (RR), are major signal transduction devices in bacteria. Typically the signal triggers HK autophosphorylation at one His residue, followed by phosphoryl transfer from the phospho-His to an Asp residue in the RR. Signal extinction frequently involves phospho-RR dephosphorylation by a phosphatase activity of the HK. Our understanding of these reactions and of the determinants of partner specificity among HK-RR couples has been greatly increased by recent crystal structures and biochemical experiments on HK-RR complexes. Cis-autophosphorylation (one subunit phosphorylates itself) occurs in some HKs while trans-autophosphorylation takes place in others. We re... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4088271 Tue, 12 Oct 2010 23:00:00 +0100 4088271 http://www.medworm.com/index.php?rid=4088270&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20951028%26dopt%3DAbstract Authors: Malabanan MM, Amyes TL, Richard JP Triosephosphate isomerase (TIM), glycerol 3-phosphate dehydrogenase, and orotidine 5'-monophosphate decarboxylase each use the binding energy from the interaction of phosphite dianion with a flexible phosphate gripper loop to activate a second, phosphodianion-truncated, substrate towards enzyme-catalyzed proton transfer, hydride transfer, and decarboxylation, respectively. Studies on TIM suggest that the most important general effect of loop closure over the substrate phosphodianion, and the associated conformational changes, is to extrude water from the enzyme active site. This should cause a decrease in the effective active-site dielectric constant, and an increase in transition state stabilization from enhanced electrostatic interactions w... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4088270 Tue, 12 Oct 2010 23:00:00 +0100 4088270 http://www.medworm.com/index.php?rid=4061863&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20934872%26dopt%3DAbstract Authors: de Jonge MD, Vogt S Hard X-ray fluorescence microscopy is well-suited to in-situ investigations of trace metal distributions within whole, unstained, biological tissue, with sub-parts-per-million detection achievable in whole cells. The high penetration of X-rays indicates the use of X-ray fluorescence tomography for structural visualization, and recent measurements have realised sub-500-nm tomography on a 10-μm cell. Limitations of present approaches impact the duration of an experiment and imaging fidelity. Developments in X-ray resolution, detector speed, cryogenic environments, and the incorporation of auxiliary signals are being pursued within the synchrotron community. Several complementary approaches to X-ray fluorescence tomography will be routinely available to the b... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4061863 Thu, 07 Oct 2010 23:00:00 +0100 4061863 http://www.medworm.com/index.php?rid=4042499&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20888754%26dopt%3DAbstract Authors: Torres FE, Recht MI, Coyle JE, Bruce RH, Williams G Higher throughput thermodynamic measurements can provide value in structure-based drug discovery during fragment screening, hit validation, and lead optimization. Enthalpy can be used to detect and characterize ligand binding, and changes that affect the interaction of protein and ligand can sometimes be detected more readily from changes in the enthalpy of binding than from the corresponding free-energy changes or from protein-ligand structures. Newer, higher throughput calorimeters are being incorporated into the drug discovery process. Improvements in titration calorimeters come from extensions of a mature technology and face limitations in scaling. Conversely, array calorimetry, an emerging technology, shows promise for s... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4042499 Wed, 29 Sep 2010 23:00:00 +0100 4042499 http://www.medworm.com/index.php?rid=4042500&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20888218%26dopt%3DAbstract Authors: McDonough MA, Loenarz C, Chowdhury R, Clifton IJ, Schofield CJ 2-Oxoglutarate and ferrous iron-dependent oxygenases have emerged as an important family of human enzymes that catalyse hydroxylations and related demethylation reactions. Their substrates in humans include proteins, nucleic acids, lipids and small molecules. They play roles in collagen biosynthesis, hypoxic sensing, regulation of gene expression and lipid biosynthesis/metabolism. Structural analyses, principally employing crystallography, have revealed that all of these oxygenases possess a double-stranded β-helix core fold that supports a highly conserved triad of iron binding residues and a less well conserved 2-oxoglutarate co-substrate binding site. The 2-oxoglutarate binds to the iron in a bidentate manner v... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4042500 Tue, 28 Sep 2010 23:00:00 +0100 4042500 http://www.medworm.com/index.php?rid=4042501&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20884198%26dopt%3DAbstract Authors: Hasnain SS, Wakatsuki S PMID: 20884198 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4042501 Mon, 27 Sep 2010 23:00:00 +0100 4042501 http://www.medworm.com/index.php?rid=4026366&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20880695%26dopt%3DAbstract Authors: Zimmerman ES, Schulman BA, Zheng N The cullin-RING ubiquitin ligases (CRLs) are the largest family of multi-subunit E3 ligases in eukaryotes, which ubiquitinate protein substrates in numerous cellular pathways. CRLs share a common arched scaffold and a RING domain catalytic subunit, but use different adaptors and substrate receptors to assemble unique E3 machineries. In comparison to the first CRL structure, recent findings have revealed increased complexity in the overall architecture and assembly mode of CRLs, including multi-domain organization, inter-domain flexibility, and subunit dimerization. These features highlight the capacity of CRLs to catalyze protein ubiquitination under distinct cellular contexts and in response to diverse signals. As the first installment of a ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4026366 Sun, 26 Sep 2010 23:00:00 +0100 4026366 http://www.medworm.com/index.php?rid=4003504&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20870402%26dopt%3DAbstract Authors: Gai D, Chang YP, Chen XS Genomic DNA replication is a necessary step in the life cycles of all organisms. To initiate DNA replication, the double-stranded DNA (dsDNA) at the origin of replication must be separated or melted; this melted region is propagated and a mature replication fork is formed. To accomplish origin recognition, initial DNA melting, and the eventual formation of a replication fork, coordinated activity of initiators, helicases, and other cellular factors are required. In this review, we focus on recent advances in the structural and biochemical studies of the initiators and the replicative helicases in multiple replication systems, with emphasis on the systems in archaeal and eukaryotic cells. These studies have yielded insights into the plausible mechanisms... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4003504 Thu, 23 Sep 2010 23:00:00 +0100 4003504 http://www.medworm.com/index.php?rid=4003584&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20869868%26dopt%3DAbstract Authors: Larabell CA, Nugent KA X-ray imaging of biological samples is progressing rapidly. In this paper we review the progress to date in high-resolution imaging of cellular architecture. In particular we survey the progress in soft X-ray tomography and argue that the field is coming of age and that important biological insights are starting to emerge. We then review the new ideas based on coherent diffraction. These methods are at a much earlier stage of development but, as they eliminate the need for X-ray optics, have the capacity to provide substantially better spatial resolution than zone plate-based methods. PMID: 20869868 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4003584 Wed, 22 Sep 2010 23:00:00 +0100 4003584 http://www.medworm.com/index.php?rid=4003785&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20850967%26dopt%3DAbstract Authors: Iwasaki K, Omura T Visualizing the viral life cycle in the host challenges us to extend our understanding of the viral infection mechanism. Three-dimensional images obtained by advanced electron tomographic imaging techniques, if resolved to molecular resolution, are helpful for bridging the atomic structural information of proteins to cellular events. Characteristic large structures appear in virus-infected host cells through the life cycle of various viruses. These structures are likely to provide clues to understanding viral infection mechanisms, such as how viruses move in host cells, how they are assembled, how they egress and how they spread cell-to-cell. Here we review recent advances in the studies of the molecular architecture of virus machinery involved in the mechan... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=4003785 Wed, 15 Sep 2010 23:00:00 +0100 4003785 http://www.medworm.com/index.php?rid=3981403&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20843678%26dopt%3DAbstract Authors: Boulanger MJ, Tonkin ML, Crawford J Apicomplexan parasites such as Plasmodium spp. (malaria) and Toxoplasma gondii (toxoplasmosis) are significant global pathogens of humans and animals. Unlike many intracellular bacterial and viral pathogens that rely on host cell uptake machinery to gain entry, apicomplexan parasites promote recognition, attachment and ultimately invasion of host cells through an orchestrated delivery of adhesins. While several of these adhesins are now known to target host cell glycans, only recently have atomic level insights been forthcoming. Here we review recent developments in defining detailed molecular blueprints used by these widespread pathogens to drive host cell adhesion and promote infectivity. PMID: 20843678 [PubMed - as supplied by publish... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=3981403 Sun, 12 Sep 2010 23:00:00 +0100 3981403 http://www.medworm.com/index.php?rid=3981407&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20833032%26dopt%3DAbstract Authors: Rudd T, Skidmore M, Guerrini M, Hricovini M, Powell A, Siligardi G, Yates E The glycosaminoglycan (GAG) family of linear sulphated polysaccharides are involved in most regulatory processes in the extracellular matrix of higher organisms. The relationship between GAG substitution pattern and activity, however, remains unclear and experimental evidence suggests that subtle conformational factors play an important role. The difficulty of modelling these complex charged molecules shifts the burden of investigation towards experimental techniques. Recent advances in complementary physical-chemical, particularly spectroscopy-based approaches are reviewed, together with methods for analysing the resulting complex data. The prospects for combining some of these approaches and fitting ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=3981407 Wed, 08 Sep 2010 23:00:00 +0100 3981407 http://www.medworm.com/index.php?rid=3981410&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20832292%26dopt%3DAbstract Authors: Holden HM, Cook PD, Thoden JB The biological importance of proteins and nucleic acids in the natural world is undeniable, and research efforts on these macromolecules have often overshadowed those directed at carbohydrates. It is now known, however, that carbohydrates not only play roles in energy storage and plant cell wall structure, but are also intimately involved in such processes as fertilization, the immune response, and cell adhesion. Indeed, recent years have seen an explosion in research efforts directed at uncovering and understanding new sugar moieties. The dideoxysugars and trideoxysugars, which are synthesized by a variety of bacteria, fungi, and plants, represent an especially intriguing class of carbohydrates. They are found, for example, on the lipopolysacchar... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=3981410 Tue, 07 Sep 2010 23:00:00 +0100 3981410 http://www.medworm.com/index.php?rid=3954593&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20810277%26dopt%3DAbstract Authors: Chruszcz M, Domagalski M, Osinski T, Wlodawer A, Minor W Structural genomics (SG) programs have developed during the last decade many novel methodologies for faster and more accurate structure determination. These new tools and approaches led to the determination of thousands of protein structures. The generation of enormous amounts of experimental data resulted in significant improvements in the understanding of many biological processes at molecular levels. However, the amount of data collected so far is so large that traditional analysis methods are limiting the rate of extraction of biological and biochemical information from 3D models. This situation has prompted us to review the challenges that remain unmet by SG, as well as the areas in which the potential impact of SG ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=3954593 Sun, 29 Aug 2010 23:00:00 +0100 3954593 http://www.medworm.com/index.php?rid=3954594&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20801639%26dopt%3DAbstract Authors: Ito Y, Selenko P While we appreciate the complexity of the intracellular environment as a general property of every living organism, we collectively lack the appropriate tools to analyze protein structures in a cellular context. In-cell NMR spectroscopy represents a novel biophysical tool to investigate the conformational and functional characteristics of biomolecules at the atomic level inside live cells. Here, we review recent in-cell NMR developments and provide an outlook towards future applications in prokaryotic and eukaryotic cells. We hope to thereby emphasize the usefulness of in-cell NMR techniques for cellular studies of complex biological processes and for structural analyses in native environments. PMID: 20801639 [PubMed - as supplied by publisher] (Source: Cu... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=3954594 Thu, 26 Aug 2010 23:00:00 +0100 3954594 http://www.medworm.com/index.php?rid=3911785&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20739176%26dopt%3DAbstract Authors: Miller LM, Dumas P Current efforts in structural biology aim to integrate structural information within the context of cellular organization and function. X-rays and infrared radiation stand at opposite ends of the electromagnetic spectrum and act as complementary probes for achieving this goal. Intense and bright beams are produced by synchrotron radiation, and are efficiently used in the wavelength domain extending from hard X-rays to the far-infrared (or THz) regime. While X-ray crystallography provides exquisite details on atomic structure, Fourier transform infrared microspectroscopy (FTIRM) is emerging as a spectroscopic probe and imaging tool for correlating molecular structure to biochemical dynamics and function. In this manuscript, the role of synchrotron FTIRM in br... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=3911785 Sun, 22 Aug 2010 23:00:00 +0100 3911785 http://www.medworm.com/index.php?rid=3882008&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20708922%26dopt%3DAbstract Authors: Woods RJ, Tessier MB Modern computational methods offer the tools to provide insight into the structural and dynamic properties of carbohydrate-protein complexes, beyond that provided by experimental structural biology. Dynamic properties such as the fluctuation of inter-molecular hydrogen bonds, the residency times of bound water molecules, side chain motions and ligand flexibility may be readily determined computationally. When taken with respect to the unliganded states, these calculations can also provide insight into the entropic and enthalpic changes in free energy associated with glycan binding. In addition, virtual ligand screening may be employed to predict the three dimensional (3D) structures of carbohydrate-protein complexes, given 3D structures for the components.... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=3882008 Wed, 11 Aug 2010 23:00:00 +0100 3882008 http://www.medworm.com/index.php?rid=3882009&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20708403%26dopt%3DAbstract Authors: Clarke J, Regan L PMID: 20708403 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=3882009 Tue, 10 Aug 2010 23:00:00 +0100 3882009 http://www.medworm.com/index.php?rid=3869397&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20705453%26dopt%3DAbstract Authors: Ramakrishnan B, Qasba PK Cell surface glycans play important cellular functions and are synthesized by glycosyltransferases. Structure and function studies show that the donor sugar specificity of the invertebrate beta1,4-N-acetyl-glactosaminyltransferase (beta4GalNAc-T) and the vertebrate beta1,4-galactosyltransferase I (beta4Gal-T1) are related by a single amino acid residue change. Comparison of the catalytic domain crystal structures of the beta4Gal-T1 and the alpha-polypeptidyl-GalNAc-T (alphappGalNAc-T) shows that their protein structure and sequences are similar. Therefore, it seems that the invertebrate beta4GalNAc-T and the catalytic domain of alphappGalNAc-T might have emerged from a common primordial gene. When vertebrates emerged from invertebrates, the amino acid ... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=3869397 Mon, 09 Aug 2010 23:00:00 +0100 3869397 http://www.medworm.com/index.php?rid=3869396&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20705454%26dopt%3DAbstract Authors: Brettel K, Byrdin M DNA photolyase uses visible light and a fully reduced flavin cofactor FADH(-) to repair major UV-induced lesions in DNA, the cyclobutane pyrimidine dimers (CPDs). Electron transfer from photoexcited FADH(-) to CPD, splitting of the two intradimer bonds, and back electron transfer to the transiently formed flavin radical FADH degrees occur in overall 1ns. Whereas the kinetics of FADH degrees was resolved, the DNA-based intermediates escaped unambiguous detection yet. Another light reaction, named photoactivation, reduces catalytically inactive FADH degrees to FADH(-) without implication of DNA. It involves electron hopping along a chain of three tryptophan residues in 30ps, as elucidated in detail by transient absorption spectroscopy. The same triple tryptop... Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=3869396 Mon, 09 Aug 2010 23:00:00 +0100 3869396 http://www.medworm.com/index.php?rid=3862875&cid=s_35498_62_f&fid=35498&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20702086%26dopt%3DAbstract Authors: Tate CG, Stevens RC PMID: 20702086 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology) Current Opinion in Structural Biology journals http://www.medworm.com/rss/comments.php?id=3862875 Sun, 08 Aug 2010 23:00:00 +0100 3862875