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366 records returned

The ins and outs of four-tunneled Reoviridae RNA-dependent RNA polymerases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
RNA-dependent RNA polymerases (RdRps) of the segmented double-stranded (ds) RNA viruses of the Reoviridae family exhibit distinguishing structural elements, enabling the enzymes to function within the confines of a proteinaceous core particle. These globular, cage-like polymerases are traversed by four well-defined tunnels, which not only allow template RNAs, nucleotides, and divalent cations to access the interior catalytic site, but also provide two distinct exit conduits for RNA templates and products-one leading out of the core and the other back inside the core. Although Reoviridae RdRps are intrinsically capable ...
Source: Current Opinion in Structural Biology - November 13, 2009 Category: Biology Authors: McDonald SM, Tao YJ, Patton JT Tags: Curr Opin Struct Biol Source Type: journals

RNA-dependent RNA polymerases from Flaviviridae.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Viral genome replication in Flaviviridae is carried out by a virally encoded RNA-dependent RNA polymerase (RdRp). These viruses initiate the RNA synthesis via a de novo mechanism that differs from the primer-dependent mechanism used by Picornaviridae. Like all polymerases, the structure of Flaviviridae RdRps resembles a right hand with characteristic fingers, palm, and thumb domains. Structural features that distinguish Flaviviridae RdRps from other polymerases are a large thumb domain and a C-terminal motif that encircles the active site. This domain arrangement restricts the volume of the template-binding channel, al...
Source: Current Opinion in Structural Biology - November 13, 2009 Category: Biology Authors: Choi KH, Rossmann MG Tags: Curr Opin Struct Biol Source Type: journals

Signaling mechanisms of the Mycobacterium tuberculosis receptor Ser/Thr protein kinases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Like eukaryotes, bacteria express receptor Ser/Thr protein kinases (STPKs) that initiate a wide variety of signaling networks. Recent biochemical and structural studies of the STPKs of Mycobacterium tuberculosis have revealed that bacterial and eukaryotic STPKs adopt common folds and share mechanisms of substrate recognition and regulation. Mycobacterial receptor STPKs are activated by dimerization through two distinct interfaces that promote activation-loop phosphorylation. The active STPKs phosphorylate diverse substrates within the bacterial cell, including other kinases as well as proteins involved in many central ...
Source: Current Opinion in Structural Biology - November 13, 2009 Category: Biology Authors: Alber T Tags: Curr Opin Struct Biol Source Type: journals

RNA polymerase fidelity and transcriptional proofreading.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Whereas mechanisms underlying the fidelity of DNA polymerases (DNAPs) have been investigated in detail, RNA polymerase (RNAP) fidelity mechanisms remained poorly understood. New functional and structural studies now suggest how RNAPs select the correct nucleoside triphosphate (NTP) substrate to prevent transcription errors, and how the enzymes detect and remove a misincorporated nucleotide during proofreading. Proofreading begins with fraying of the misincorporated nucleotide away from the DNA template, which pauses transcription. Subsequent backtracking of RNAP by one position enables nucleolytic cleavage of an RNA di...
Source: Current Opinion in Structural Biology - November 12, 2009 Category: Biology Authors: Sydow JF, Cramer P Tags: Curr Opin Struct Biol Source Type: journals

Structural insights into replication initiation and elongation processes by the FMDV RNA-dependent RNA polymerase.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
RNA-dependent RNA polymerases (RdRPs) play central roles in both transcription and viral genome replication. In picornaviruses, these functions are catalyzed by the virally encoded RdRP, termed 3D. Polymerase 3D also catalyzes the covalent linkage of UMP to a tyrosine on the small protein VPg. Uridylylated VPg then serves as a protein primer for the initiation of RNA synthesis. Seven different crystal structures of foot-and-mouth disease virus (FMDV) 3D catalytic complexes have enhanced our understanding of template and primer recognition, VPg uridylylation, and rNTP binding and catalysis. Such structural information i...
Source: Current Opinion in Structural Biology - November 12, 2009 Category: Biology Authors: Ferrer-Orta C, Agudo R, Domingo E, Verdaguer N Tags: Curr Opin Struct Biol Source Type: journals

Forks, pincers, and triggers: the tools for nucleotide incorporation and translocation in multi-subunit RNA polymerases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present a facilitated Brownian ratchet model of nucleotide incorporation, in which templated NTP binding to a non-catalytic site in the main channel promotes the conformational changes that lead to opening of the catalytic site and translocation. PMID: 19913407 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology)
Source: Current Opinion in Structural Biology - November 11, 2009 Category: Biology Authors: Erie DA, Kennedy SR Tags: Curr Opin Struct Biol Source Type: journals

Dynamics: the missing link between structure and function of the viral RNA-dependent RNA polymerase?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The structural basis for nucleotide incorporation fidelity remains an open question for all nucleic acid polymerases. Addressing this question for the viral RNA-dependent RNA polymerase (RdRp) is of particular, practical significance because it is a determinant of sensitivity to antiviral nucleosides and may be a determinant of viral virulence. All polymerases are thought to employ the same catalytic mechanism, but the rate of nucleotide incorporation can vary substantially. Here we review some of the recent work with the RdRp that leads us to suggest that structure provides only a partial understanding of RdRp functio...
Source: Current Opinion in Structural Biology - November 10, 2009 Category: Biology Authors: Cameron CE, Moustafa IM, Arnold JJ Tags: Curr Opin Struct Biol Source Type: journals

RNA-dependent RNA polymerases from flaviviruses and Picornaviridae.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Flaviviruses and picornaviruses are positive-strand RNA viruses that encode the RNA-dependent RNA polymerase (RdRp) required for replicating the viral genome in infected cells. Because of their specific and essential role in the virus life cycle, RdRps are prime targets for antiviral drugs. Recent structural data have shed light on the different strategies used by RdRps from flaviviruses and Picornaviridae to initiate RNA polymerization. New details about the catalytic mechanism, the role of metal ions, how these RdRps interact with other nonstructural (NS) viral and host-cell proteins as well as with the viral RNA gen...
Source: Current Opinion in Structural Biology - November 10, 2009 Category: Biology Authors: Lescar J, Canard B Tags: Curr Opin Struct Biol Source Type: journals

Proteins: how RNA polymerases work.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19910185 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology)
Source: Current Opinion in Structural Biology - November 10, 2009 Category: Biology Authors: Cramer P, Arnold E Tags: Curr Opin Struct Biol Source Type: journals

Elongation by RNA polymerase: a race through roadblocks.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Transcription is the first and most regulated step of gene expression. RNA polymerase (RNAP) is the heart of the transcription machinery and a major target for numerous regulatory pathways in living cells. The crystal structures of transcription complexes formed by bacterial RNAP in various configurations have provided a number of breakthroughs in understanding basic, universal mechanisms of transcription and have revealed regulatory 'hot spots' in RNAP that serve as targets and anchors for auxiliary transcription factors. In combination with biochemical analyses, these structures allow feasible modeling of the regulat...
Source: Current Opinion in Structural Biology - November 4, 2009 Category: Biology Authors: Vassylyev DG Tags: Curr Opin Struct Biol Source Type: journals

The oxygen-binding vs. oxygen-consuming paradigm in biocatalysis: structural biology and biomolecular simulation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Oxygen biocatalysis and regulation is crucial to a variety of biochemical processes in nature. Oxygen-binding proteins cover only a limited part of oxygen biocatalysis, which involves numerous examples of oxygen-consuming biocatalysts with low oxygen affinities. The integration of experiments with powerful biomolecular simulation opens appealing possibilities to investigate crucial questions on the fascinating relationship between enzyme dynamics and oxygen biocatalysis in new protein structures. PMID: 19896366 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology)
Source: Current Opinion in Structural Biology - November 4, 2009 Category: Biology Authors: Baron R, McCammon JA, Mattevi A Tags: Curr Opin Struct Biol Source Type: journals

Structure-function analysis of RNA polymerases I and III.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent advances in elucidating the structure of yeast Pol I and III are based on a combination of X-ray crystal analysis, electron microscopy and homology modelling. They allow a better comparison of the three eukaryotic nuclear RNA polymerases, underscoring the most obvious difference existing between the three enzymes, which lies in the existence of additional Pol-I-specific and Pol-III-specific subunits. Their location on the cognate RNA polymerases is now fairly well known, suggesting precise hypotheses as to their function in transcription during initiation, elongation, termination and/or reinitiation. Unexpectedl...
Source: Current Opinion in Structural Biology - November 4, 2009 Category: Biology Authors: Werner M, Thuriaux P, Soutourina J Tags: Curr Opin Struct Biol Source Type: journals

Macromolecular micromovements: how RNA polymerase translocates.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Multi-subunit DNA-dependent RNA polymerases synthesize RNA molecules thousands of nucleotides long. The reiterative reaction of nucleotide condensation occurs at rates of tens of nucleotides per second, invariably linked to the translocation of the enzyme along the DNA template, or threading of the DNA and the nascent RNA molecule through the enzyme. Reiteration of the nucleotide addition/translocation cycle without dissociation from the DNA and RNA requires both isomorphic and metamorphic conformational flexibility of a magnitude substantial enough to accommodate the requisite molecular motions. Here we review some of...
Source: Current Opinion in Structural Biology - November 2, 2009 Category: Biology Authors: Svetlov V, Nudler E Tags: Curr Opin Struct Biol Source Type: journals

Markers of fitness in a successful enzyme superfamily.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Haloalkanoic acid dehalogenase (HAD) superfamily members serve as the predominant catalysts of metabolic phosphate ester hydrolysis in all three superkingdoms of life. Collectively, the known structural, bioinformatic, and mechanistic data offer a glimpse of the variety of HAD enzymes that have evolved in the service of metabolic expansion. Factors that have contributed to superfamily dominance include a chemically versatile nucleophile, stability of the core superfold, structural modularity of the chemistry and specificity domains, conformational coupling conferred by the topology of the inserted specificity elements,...
Source: Current Opinion in Structural Biology - November 2, 2009 Category: Biology Authors: Allen KN, Dunaway-Mariano D Tags: Curr Opin Struct Biol Source Type: journals

Archaeal RNA polymerase.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The recently solved X-ray crystal structures of archaeal RNA polymerase (RNAP) allow a structural comparison of the transcription machinery among all three domains of life. Archaeal transcription is very simple and all components, including the structures of general transcription factors and RNAP, are highly conserved in eukaryotes. Therefore, it could be a new model for the dissection of the eukaryotic transcription apparatus. The archaeal RNAP structure also provides a framework for addressing the functional role that Fe-S clusters play within the transcription machinery of archaea and eukaryotes. A comparison betwee...
Source: Current Opinion in Structural Biology - October 30, 2009 Category: Biology Authors: Hirata A, Murakami KS Tags: Curr Opin Struct Biol Source Type: journals

Adenylate-forming enzymes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Thioesters, amides, and esters are common chemical building blocks in a wide array of natural products. The formation of these bonds can be catalyzed in a variety of ways. For chemists, the use of an activating group is a common strategy and adenylate enzymes are exemplars of this approach. Adenylating enzymes activate the otherwise unreactive carboxylic acid by transforming the normal hydroxyl leaving group into adenosine monophosphate. Recently there have been a number of studies of such enzymes and in this review we suggest a new classification scheme. The review highlights the diversity in enzyme fold, active site ...
Source: Current Opinion in Structural Biology - October 14, 2009 Category: Biology Authors: Schmelz S, Naismith JH Tags: Curr Opin Struct Biol Source Type: journals

Selected topics from the advancing forefront of glycoprotein and glycolipid research.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19822415 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology)
Source: Current Opinion in Structural Biology - October 9, 2009 Category: Biology Authors: Sharon N, Gallagher J Tags: Curr Opin Struct Biol Source Type: journals

Biophysical methods.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19822416 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology)
Source: Current Opinion in Structural Biology - October 9, 2009 Category: Biology Authors: Moffat K, Engel A Tags: Curr Opin Struct Biol Source Type: journals

Force and function: probing proteins with AFM-based force spectroscopy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Forces play a pivotal role in life, and the response of live systems to forces requires molecules and molecular interactions with adequate properties to counteract both in a passive and also, if needed, in an active, dynamic manner. However, at the level of individual molecules these forces are so minute, that the development of sophisticated experiments to measure and control them was required. With the maturation of these techniques, particularly the AFM-based single-molecule force spectroscopy into commercial instruments, the scope has widened considerably and more and more studies shed light onto the different aspe...
Source: Current Opinion in Structural Biology - October 9, 2009 Category: Biology Authors: Puchner EM, Gaub HE Tags: Curr Opin Struct Biol Source Type: journals

The structural changes of T7 RNA polymerase from transcription initiation to elongation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The structures of T7 RNA polymerase (T7 RNAP) captured in the initiation and elongation phases of transcription, as well as an intermediate stage provide insights into how this RNA polymerase protein can initiate RNA synthesis and synthesize 7-10 nucleotides of RNA while remaining bound to the DNA promoter site. Recently, the structures of T7 RNAP bound to its promoter DNA along with either a seven nucleotide or eight nucleotide transcript show an elongated product site resulting from a 40 degrees or 45 degrees rotation of the promoter and domain that binds it. The different functional properties of the initiation and ...
Source: Current Opinion in Structural Biology - October 4, 2009 Category: Biology Authors: Steitz TA Tags: Curr Opin Struct Biol Source Type: journals

Carbohydrate recognition by the mannose-6-phosphate receptors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The two P-type lectins, the 46kDa cation-dependent mannose-6-phosphate (Man-6-P) receptor (CD-MPR), and the 300kDa cation-independent Man-6-P receptor (CI-MPR), are the founding members of the growing family of mannose-6-phosphate receptor homology (MRH) proteins. A major cellular function of the MPRs is to transport Man-6-P-containing acid hydrolases from the Golgi to endosomal/lysosomal compartments. Recent advances in the structural analyses of both CD-MPR and CI-MPR have revealed the structural basis for phosphomannosyl recognition by these receptors and provided insights into how the receptors load and unload thei...
Source: Current Opinion in Structural Biology - October 1, 2009 Category: Biology Authors: Kim JJ, Olson LJ, Dahms NM Tags: Curr Opin Struct Biol Source Type: journals

The molecular basis and functional implications of chemokine interactions with heparan sulphate.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The ability of cells to migrate in response to chemokine mediated signals, a process known as chemotaxis, is fundamental in the context of inflammation, as in many other physiological processes. Chemokines binding to heparan sulphate ensures their correct positioning within tissues and maintains haptotactic gradients along which cell can migrate directionally. In this survey, some structural aspects of the chemokine-heparan sulphate interface are described, with a focus on CXCL12; alternative splicing of which finely tunes its affinity for glycosaminoglycans, through the generation of an intrinsically disordered peptid...
Source: Current Opinion in Structural Biology - September 29, 2009 Category: Biology Authors: Lortat-Jacob H Tags: Curr Opin Struct Biol Source Type: journals

Mass spectrometry of large complexes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mass spectrometry is becoming a more and more powerful tool for investigating protein complexes. Recent developments, based on different ionization techniques, electrospray, desorption/ionization and others are contributing to the usefulness of MS to describe the organization and structure of large non-covalent assemblies. PMID: 19782560 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology)
Source: Current Opinion in Structural Biology - September 23, 2009 Category: Biology Authors: Bich C, Zenobi R Tags: Curr Opin Struct Biol Source Type: journals

Single DNA/protein studies with magnetic traps.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Magnetic traps provide a simple technique to pull and twist a variety of biomolecules and monitor the resulting change in extension. They have been used with great success to investigate the interaction of stretched and supercoiled DNA and DNA fibers (e.g. chromatin) with a great variety of enzymes. In this small review we will address their recent use in the study of topoisomerases, gyrase, DNA translocases and various structural proteins. PMID: 19783425 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology)
Source: Current Opinion in Structural Biology - September 21, 2009 Category: Biology Authors: Meglio A, Praly E, Ding F, Allemand JF, Bensimon D, Croquette V Tags: Curr Opin Struct Biol Source Type: journals

Exploring conformational modes of macromolecular assemblies by multiparticle cryo-EM.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Single particle cryo-electron microscopy (cryo-EM) is a technique aimed at structure determination of large macromolecular complexes in their unconstrained, physiological conditions. The power of the method has been demonstrated in selected studies where for highly symmetric molecules the resolution attained permitted backbone tracing. However, most molecular complexes appear to exhibit intrinsic conformational variability necessary to perform their functions. Therefore, it is now increasingly recognized that sample heterogeneity constitutes a major methodological challenge for cryo-EM. To overcome it dedicated experim...
Source: Current Opinion in Structural Biology - September 17, 2009 Category: Biology Authors: Spahn CM, Penczek PA Tags: Curr Opin Struct Biol Source Type: journals

Stability effects of mutations and protein evolvability.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe ways of predicting and analyzing stability effects of mutations, and mechanisms that buffer or compensate for these destabilizing effects and thereby promote protein evolvabilty, in nature and in the laboratory. PMID: 19765975 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology)
Source: Current Opinion in Structural Biology - September 15, 2009 Category: Biology Authors: Tokuriki N, Tawfik DS Tags: Curr Opin Struct Biol Source Type: journals

High-throughput crystallography for structural genomics.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this report we focus mainly on reviewing structural genomics high-throughput X-ray crystallography technologies and their impact. PMID: 19765976 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology)
Source: Current Opinion in Structural Biology - September 15, 2009 Category: Biology Authors: Joachimiak A Tags: Curr Opin Struct Biol Source Type: journals

From biomolecular structure to functional understanding: new NMR developments narrow the gap.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article discusses recent advances and applications. PMID: 19716691 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology)
Source: Current Opinion in Structural Biology - August 26, 2009 Category: Biology Authors: Grzesiek S, Sass HJ Tags: Curr Opin Struct Biol Source Type: journals

Membranes Editorial overview.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19709877 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology)
Source: Current Opinion in Structural Biology - August 23, 2009 Category: Biology Authors: Doyle DA, Shipley GG Tags: Curr Opin Struct Biol Source Type: journals

Recent developments in phasing and structure refinement for macromolecular crystallography.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Central to crystallographic structure solution is obtaining accurate phases in order to build a molecular model, ultimately followed by refinement of that model to optimize its fit to the experimental diffraction data and prior chemical knowledge. Recent advances in phasing and model refinement and validation algorithms make it possible to arrive at better electron density maps and more accurate models. PMID: 19700309 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology)
Source: Current Opinion in Structural Biology - August 20, 2009 Category: Biology Authors: Adams PD, Afonine PV, Grosse-Kunstleve RW, Read RJ, Richardson JS, Richardson DC, Terwilliger TC Tags: Curr Opin Struct Biol Source Type: journals

Sialic acids as regulators of molecular and cellular interactions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The wide occurrence of sialic acids (Sia) in various chemical forms linked as monomers or polymers in an outstanding position in a multitude of complex carbohydrates of animals and microorganisms renders them as most versatile function modulators in cell biology and pathology. A survey is presented of recent advances in the study of the influences that Sias have as bulky hydrophilic and electronegatively charged monosaccharides on animal cells and on their interaction with microorganisms. Some highlights are: sialylation leads to increased anti-inflammatory activity of IgG antibodies, facilitates the escape of microorg...
Source: Current Opinion in Structural Biology - August 18, 2009 Category: Biology Authors: Schauer R Tags: Curr Opin Struct Biol Source Type: journals

Editorial overview-engineering and design.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19683427 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology)
Source: Current Opinion in Structural Biology - August 12, 2009 Category: Biology Authors: Kuhlman B, F Degrado W Tags: Curr Opin Struct Biol Source Type: journals

Engineering G protein-coupled receptors to facilitate their structure determination.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Over the last two years, 10 new high-resolution structures of G protein-coupled receptors (GPCRs), either with antagonist bound or in an active-like state, have been solved. Whilst the structures of bovine opsin and squid rhodopsin were determined using protein purified from native sources, a rhodopsin mutant structure, the structures of the beta(1) and beta(2) adrenergic receptors and the adenosine A(2a) receptor were determined from engineered protein heterologously expressed in either insect or mammalian cells. These results are the culmination of years of careful work and have resulted in three new strategies for s...
Source: Current Opinion in Structural Biology - August 11, 2009 Category: Biology Authors: Tate CG, Schertler GF Tags: Curr Opin Struct Biol Source Type: journals

Lipopeptide detergents for membrane protein studies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
An ideal detergent would be able to maintain a membrane protein in a soluble state with no measurable effect on the functional, structural, and thermodynamic properties of the protein relative to the bilayer-embedded state. Unfortunately, the detergents that are commonly used by membrane protein biochemists fall short of this standard. Although remarkable advances have been made in membrane protein structural biology, there remains a need for improved detergents that provide a more natural substitute for the membrane environment. Lipopeptide detergents (LPDs) are a new class of amphiphile designed to be better mimics o...
Source: Current Opinion in Structural Biology - August 11, 2009 Category: Biology Authors: Privé GG Tags: Curr Opin Struct Biol Source Type: journals

Lipid-protein interactions probed by electron crystallography.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Electron crystallography is arguably the only electron cryomicroscopy (cryoEM) technique able to deliver an atomic-resolution structure of membrane proteins embedded in the lipid bilayer. In the electron crystallographic structures of the light driven ion pump, bacteriorhodopsin, and the water channel, aquaporin-0, sufficiently high resolution was obtained and both lipid and protein were visualized, modeled, and described in detail. An extensive network of lipid-protein interactions mimicking native membranes is established and maintained in two-dimensional (2D) crystalline vesicles used for structural analysis by elec...
Source: Current Opinion in Structural Biology - August 10, 2009 Category: Biology Authors: Reichow SL, Gonen T Tags: Curr Opin Struct Biol Source Type: journals

The role of solution NMR in the structure determinations of VDAC-1 and other membrane proteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The voltage-dependent anion channel (VDAC) is an essential protein in the eukaryotic outer mitochondrial membrane, providing the pore for substrate diffusion. Three high-resolution structures of the isoform 1 of VDAC in detergent micelles and bicelles have recently been published, using solution NMR and X-ray crystallography. They resolve longstanding discussions about the membrane topology of VDAC and provide the first eukaryotic beta-barrel membrane protein structure. The structure contains a surprising feature that had not been observed in an integral membrane protein before: A parallel beta-strand pairing and thus ...
Source: Current Opinion in Structural Biology - August 6, 2009 Category: Biology Authors: Hiller S, Wagner G Tags: Curr Opin Struct Biol Source Type: journals

Transmembrane vs. non-transmembrane hydrophobic helix topography in model and natural membranes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Experimental studies have begun to define how formation of transmembrane (TM) vs. non-TM hydrophobic helix topographies is controlled. It has been found that topography is very sensitive to sequence and lipid structure. Interestingly, there is a broad agreement between studies using artificial model membranes and natural membranes. These studies provide important insights into membrane protein insertion and function. PMID: 19665887 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology)
Source: Current Opinion in Structural Biology - August 6, 2009 Category: Biology Authors: London E, Shahidullah K Tags: Curr Opin Struct Biol Source Type: journals

Folding of glycoproteins: toward understanding the biophysics of the glycosylation code.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Glycosylation is among the most common post-translational modifications that proteins undergo that may affect many of their activities. It may also modify the underlying energy landscape of glycoproteins in a way that their altered biophysical characteristics are linked to their bioactivity. Yet, the capability of glycosylation to modify thermodynamic and kinetic properties varies greatly between glycoproteins. Deciphering the 'glycosylation code' that dictates the interplay between the nature of the carbohydrates or the proteins and the biophysical properties of the glycosylated proteins is essential. In this article,...
Source: Current Opinion in Structural Biology - July 30, 2009 Category: Biology Authors: Shental-Bechor D, Levy Y Tags: Curr Opin Struct Biol Source Type: journals

Computational design of affinity and specificity at protein-protein interfaces.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The computer-based design of protein-protein interactions is a rigorous test of our understanding of molecular recognition and an attractive approach for creating novel tools for cell and molecular research. Considerable attention has been placed on redesigning the affinity and specificity of naturally occurring interactions. Several studies have shown that reducing the desolvation costs for binding while preserving shape complimentarity and hydrogen bonding is an effective strategy for improving binding affinities. In favorable cases specificity has been designed by focusing only on interactions with the target protei...
Source: Current Opinion in Structural Biology - July 28, 2009 Category: Biology Authors: Karanicolas J, Kuhlman B Tags: Curr Opin Struct Biol Source Type: journals

Membrane protein structure determination using cryo-electron tomography and 3D image averaging.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The vast majority of membrane protein complexes of biological interest cannot be purified to homogeneity, or removed from a physiologically relevant context without loss of function. It is therefore not possible to easily determine the 3D structures of these protein complexes using X-ray crystallography or conventional cryo-electron microscopy. Newly emerging methods that combine cryo-electron tomography with 3D image classification and averaging are, however, beginning to provide unique opportunities for in situ determination of the structures of membrane protein assemblies in intact cells and nonsymmetric viruses. He...
Source: Current Opinion in Structural Biology - July 28, 2009 Category: Biology Authors: Bartesaghi A, Subramaniam S Tags: Curr Opin Struct Biol Source Type: journals

A prokaryotic perspective on pentameric ligand-gated ion channel structure.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The X-ray structures of two prokaryotic pentameric ligand-gated ion channels have recently provided detailed insight into this important family of neurotransmitter receptors. These prokaryotic homologs share the overall architecture of their eukaryotic counterparts with conservation in functionally important residues. Although both structures are similar they show distinct conformations of the ion conduction pore. One structure depicts a nonconducting state of the channel with a narrow transmembrane pore that is interrupted by conserved hydrophobic residues. The second structure reveals a conducting conformation where ...
Source: Current Opinion in Structural Biology - July 28, 2009 Category: Biology Authors: Hilf RJ, Dutzler R Tags: Curr Opin Struct Biol Source Type: journals

Structural snapshots of conformational changes in a seven-helix membrane protein: lessons from bacteriorhodopsin.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent advances in crystallizing integral membrane proteins have led to atomic models for the structures of several seven-helix membrane proteins, including those in the G-protein-coupled receptor family. Further steps toward exploring structure-function relationships will undoubtedly involve determination of the structural changes that occur during the various stages of receptor activation and deactivation. We expect that these efforts will bear many parallels to the studies of conformational changes in bacteriorhodopsin, which still remains the best-studied seven-helix membrane protein. Here, we provide a brief revie...
Source: Current Opinion in Structural Biology - July 27, 2009 Category: Biology Authors: Hirai T, Subramaniam S, Lanyi JK Tags: Curr Opin Struct Biol Source Type: journals

Peptides as materials.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe recent efforts to add electronically active groups, such as metal complexes and various porphyrin derivatives, onto peptide-based materials. Having created such materials, the next challenge in creating a nanocircuit is to deposit these materials robustly and precisely onto appropriate surfaces. Methods for the deposition of peptides onto a variety of inorganic and organic surfaces are explored. Advances in patterning at the nanoscale are also described, focusing largely on softer methods appropriate for peptides. There are challenges yet to be overcome in realizing such peptide-based nanocircuits; these are di...
Source: Current Opinion in Structural Biology - July 27, 2009 Category: Biology Authors: Pepe-Mooney BJ, Fairman R Tags: Curr Opin Struct Biol Source Type: journals

Peptides in the treatment of AIDS.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Fusion of HIV-1 and target cells is mediated by the envelope protein gp41 that undergoes a series of conformational changes during the process of infection. Knowledge of the structural biology of gp41 allows the design of potent peptide inhibitors that prevent the virus from entering lymphocytes and macrophages. The design of such inhibitors is the subject of this review. PMID: 19632107 [PubMed - as supplied by publisher] (Source: Current Opinion in Structural Biology)
Source: Current Opinion in Structural Biology - July 22, 2009 Category: Biology Authors: Naider F, Anglister J Tags: Curr Opin Struct Biol Source Type: journals

Structure and function of Na(+)-symporters with inverted repeats.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
[Nelson N: The family of Na(+)/Cl(-)neurotransmitter transporters. J Neurochem 1998, 71:1786-1803; Wright EM, Turk E: The sodium glucose cotransport family SLC5. Pflugers Arch 2004: 510-518; Turk E, Wright EM: Membrane topology motifs in the SGLT cotransporter family. J Membr Biol 1997, 159:1-20; Chen NH, Reith ME, Quick MW: Synaptic uptake and beyond: the sodium- and chloride-dependent neurotransmitter transporter family SLC6. Pflugers Arch 2004, 447:519-531]. [Yamashita A, Singh SK, Kawate T, Jin Y, Gouaux E: Crystal structure of a bacterial homologue of Na(+)/Cl(-)-dependent neurotransmitter transporters. Nature 200...
Source: Current Opinion in Structural Biology - July 21, 2009 Category: Biology Authors: Abramson J, Wright EM Tags: Curr Opin Struct Biol Source Type: journals

Glycoprotein folding, quality control and ER-associated degradation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Nascent N-linked glycoproteins possess a large oligosaccharide precursor, Glc(3)Man(9)GlcNAc(2), which is later sequentially trimmed. Recent studies help understand the code displayed by each structure produced by this trimming and its decoding by lectins. The calnexin folding cycle targets only monoglucosylated oligosaccharides. N-glycans of misfolded glycoproteins are then more extensively trimmed than once thought, being targeted for degradation by removal of three or four mannose residues. A high local concentration of endoplasmic reticulum (ER) mannosidase I in an ER-derived quality control compartment is mainly r...
Source: Current Opinion in Structural Biology - July 16, 2009 Category: Biology Authors: Lederkremer GZ Tags: Curr Opin Struct Biol Source Type: journals

Gangliosides in cell recognition and membrane protein regulation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Gangliosides, sialic acid-bearing glycosphingolipids, are expressed on all vertebrate cells, and are the major glycans on nerve cells. They are anchored to the plasma membrane through their ceramide lipids with their varied glycans extending into the extracellular space. Through sugar-specific interactions with glycan-binding proteins on apposing cells, gangliosides function as receptors in cell-cell recognition, regulating natural killer cell cytotoxicity via Siglec-7, myelin-axon interactions via Siglec-4 (myelin-associated glycoprotein), and inflammation via E-selectin. Gangliosides also interact laterally in their ...
Source: Current Opinion in Structural Biology - July 13, 2009 Category: Biology Authors: Lopez PH, Schnaar RL Tags: Curr Opin Struct Biol Source Type: journals

Membrane protein crystallization from lipidic phases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Membrane protein structural biology is enjoying a steady acceleration in the rate of success. Nevertheless, numerous membrane protein targets are resistant to the traditional approach of directly crystallizing detergent solubilized and purified protein and the 'niche market' of lipidic phase crystallization is emerging as a powerful complement. These approaches, including lipidic cubic phase, lipidic sponge phase, and bicelle crystallization methods, all immerse purified membrane protein within a lipid rich matrix before crystallization. This environment is hypothesized to contribute to the protein's long-term structur...
Source: Current Opinion in Structural Biology - July 3, 2009 Category: Biology Authors: Johansson LC, Wöhri AB, Katona G, Engström S, Neutze R Tags: Curr Opin Struct Biol Source Type: journals

Mass spectrometry in the analysis of N-linked and O-linked glycans.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mass spectrometry (MS) continues to play a vital role in defining the structures of N-glycans and O-glycans in glycoproteins via glycomic and glycoproteomic methodologies. The former seeks to define the total N-glycan and/or O-glycan repertoire in a biological sample whilst the latter is concerned with the analysis of glycopeptides. Recent technical developments have included improvements in tandem mass spectrometry (MS/MS and MS(n)) sequencing methodologies, more sensitive methods for analysing sulfated and polysialylated glycans and better procedures for defining the sites of O-glycosylation. New tools have been intr...
Source: Current Opinion in Structural Biology - July 2, 2009 Category: Biology Authors: North SJ, Hitchen PG, Haslam SM, Dell A Tags: Curr Opin Struct Biol Source Type: journals

Neutralizing ebolavirus: structural insights into the envelope glycoprotein and antibodies targeted against it.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The ebolavirus (EBOV) envelope glycoprotein (GP) is solely responsible for viral attachment to, fusion with, and entry of new host cells, and consequently is a major target of vaccine design efforts. Recently determined crystal structures of key antibodies in complex with their EBOV epitopes have provided insights into the molecular architecture of GP and defined likely hotspots for viral neutralization. In this review, we discuss the structural basis for antibody-mediated neutralization of ebolavirus and its implications for novel therapeutic or vaccine strategies. PMID: 19559599 [PubMed - as supplied by publisher...
Source: Current Opinion in Structural Biology - June 23, 2009 Category: Biology Authors: Lee JE, Saphire EO Tags: Curr Opin Struct Biol Source Type: journals