Single-molecule FRET probes allosteric effects on protein-translocating pore loops of a AAA+ machine
Biophys J. 2024 Feb 6;123(3):374-388. doi: 10.1016/j.bpj.2024.01.002. Epub 2024 Jan 9.ABSTRACTAAA+ proteins (ATPases associated with various cellular activities) comprise a family of powerful ring-shaped ATP-dependent translocases that carry out numerous vital substrate-remodeling functions. ClpB is a AAA+ protein disaggregation machine that forms a two-tiered hexameric ring, with flexible pore loops protruding into its center and binding to substrate proteins. It remains unknown whether these pore loops contribute only passively to substrate-protein threading or have a more active role. Recently, we have applied single-mo...
Source: Biophysical Journal - January 10, 2024 Category: Physics Authors: Marija Iljina Hisham Mazal Ashan Dayananda Zhaocheng Zhang George Stan Inbal Riven Gilad Haran Source Type: research
Anomalous Coarsening of Coalescing Nucleoli in Human Cells
Biophys J. 2024 Jan 8:S0006-3495(24)00006-7. doi: 10.1016/j.bpj.2024.01.005. Online ahead of print.ABSTRACTCoarsening is a ubiquitous phenomenon in droplet systems near thermodynamic equilibrium - as an increase in droplet size lowers the system's free energy - however, coarsening of droplets in non-equilibrium systems, such as the cell nucleus, is far from understood. Liquid condensates in the cell nucleus, like nucleoli, form by liquid-liquid phase separation and play a key role in the nuclear organization. In human cells, nucleolar droplets are nucleated at the beginning of the cell cycle and coarsen with time by coales...
Source: Biophysical Journal - January 9, 2024 Category: Physics Authors: Giorgi Arsenadze Christina M Caragine Taylor Coakley Iraj Eshghi Yuwei Yang Alex Wofford Alexandra Zidovska Source Type: research
Anomalous Coarsening of Coalescing Nucleoli in Human Cells
Biophys J. 2024 Jan 8:S0006-3495(24)00006-7. doi: 10.1016/j.bpj.2024.01.005. Online ahead of print.ABSTRACTCoarsening is a ubiquitous phenomenon in droplet systems near thermodynamic equilibrium - as an increase in droplet size lowers the system's free energy - however, coarsening of droplets in non-equilibrium systems, such as the cell nucleus, is far from understood. Liquid condensates in the cell nucleus, like nucleoli, form by liquid-liquid phase separation and play a key role in the nuclear organization. In human cells, nucleolar droplets are nucleated at the beginning of the cell cycle and coarsen with time by coales...
Source: Biophysical Journal - January 9, 2024 Category: Physics Authors: Giorgi Arsenadze Christina M Caragine Taylor Coakley Iraj Eshghi Yuwei Yang Alex Wofford Alexandra Zidovska Source Type: research
Dynamics of receptor activation by agonists
Biophys J. 2024 Jan 4:S0006-3495(24)00003-1. doi: 10.1016/j.bpj.2024.01.003. Online ahead of print.ABSTRACTHow do agonists turn on receptors? The model system we have used to address this question is the adult-type skeletal muscle nicotinic acetylcholine receptor (AChR). This ligand-gated ion channel has 2 orthosteric sites (for neurotransmitters) in the extracellular domain linked to an allosteric site (a gate) in the transmembrane domain. The goal of this Perspective is to summarize how measurements of agonist binding energy reveal the dynamics of the neurotransmitter sites and the fundamental link between binding and ga...
Source: Biophysical Journal - January 5, 2024 Category: Physics Authors: Anthony Auerbach Source Type: research
Phosphomimetic substitutions in TDP-43's transiently α-helical region suppress phase separation
Biophys J. 2024 Jan 4:S0006-3495(24)00001-8. doi: 10.1016/j.bpj.2024.01.001. Online ahead of print.ABSTRACTPhosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) is present within the aggregates of several age-related neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD) and Alzheimer's disease, to the point that the presence of phosphorylated TDP-43 is considered a hallmark of some of these diseases. The majority of known TDP-43 phosphorylation sites detected in ALS/FTLD patients is located in the low complexity domain (LCD), the same domain that has been sho...
Source: Biophysical Journal - January 5, 2024 Category: Physics Authors: Raza Haider Srinivasa Penumutchu Solomiia Boyko Witold K Surewicz Source Type: research
Dynamics of receptor activation by agonists
Biophys J. 2024 Jan 4:S0006-3495(24)00003-1. doi: 10.1016/j.bpj.2024.01.003. Online ahead of print.ABSTRACTHow do agonists turn on receptors? The model system we have used to address this question is the adult-type skeletal muscle nicotinic acetylcholine receptor (AChR). This ligand-gated ion channel has 2 orthosteric sites (for neurotransmitters) in the extracellular domain linked to an allosteric site (a gate) in the transmembrane domain. The goal of this Perspective is to summarize how measurements of agonist binding energy reveal the dynamics of the neurotransmitter sites and the fundamental link between binding and ga...
Source: Biophysical Journal - January 5, 2024 Category: Physics Authors: Anthony Auerbach Source Type: research
Phosphomimetic substitutions in TDP-43's transiently α-helical region suppress phase separation
Biophys J. 2024 Jan 4:S0006-3495(24)00001-8. doi: 10.1016/j.bpj.2024.01.001. Online ahead of print.ABSTRACTPhosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) is present within the aggregates of several age-related neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD) and Alzheimer's disease, to the point that the presence of phosphorylated TDP-43 is considered a hallmark of some of these diseases. The majority of known TDP-43 phosphorylation sites detected in ALS/FTLD patients is located in the low complexity domain (LCD), the same domain that has been sho...
Source: Biophysical Journal - January 5, 2024 Category: Physics Authors: Raza Haider Srinivasa Penumutchu Solomiia Boyko Witold K Surewicz Source Type: research
Dynamics of receptor activation by agonists
Biophys J. 2024 Jan 4:S0006-3495(24)00003-1. doi: 10.1016/j.bpj.2024.01.003. Online ahead of print.ABSTRACTHow do agonists turn on receptors? The model system we have used to address this question is the adult-type skeletal muscle nicotinic acetylcholine receptor (AChR). This ligand-gated ion channel has 2 orthosteric sites (for neurotransmitters) in the extracellular domain linked to an allosteric site (a gate) in the transmembrane domain. The goal of this Perspective is to summarize how measurements of agonist binding energy reveal the dynamics of the neurotransmitter sites and the fundamental link between binding and ga...
Source: Biophysical Journal - January 5, 2024 Category: Physics Authors: Anthony Auerbach Source Type: research
Phosphomimetic substitutions in TDP-43's transiently α-helical region suppress phase separation
Biophys J. 2024 Jan 4:S0006-3495(24)00001-8. doi: 10.1016/j.bpj.2024.01.001. Online ahead of print.ABSTRACTPhosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) is present within the aggregates of several age-related neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD) and Alzheimer's disease, to the point that the presence of phosphorylated TDP-43 is considered a hallmark of some of these diseases. The majority of known TDP-43 phosphorylation sites detected in ALS/FTLD patients is located in the low complexity domain (LCD), the same domain that has been sho...
Source: Biophysical Journal - January 5, 2024 Category: Physics Authors: Raza Haider Srinivasa Penumutchu Solomiia Boyko Witold K Surewicz Source Type: research
Dynamics of receptor activation by agonists
Biophys J. 2024 Jan 4:S0006-3495(24)00003-1. doi: 10.1016/j.bpj.2024.01.003. Online ahead of print.ABSTRACTHow do agonists turn on receptors? The model system we have used to address this question is the adult-type skeletal muscle nicotinic acetylcholine receptor (AChR). This ligand-gated ion channel has 2 orthosteric sites (for neurotransmitters) in the extracellular domain linked to an allosteric site (a gate) in the transmembrane domain. The goal of this Perspective is to summarize how measurements of agonist binding energy reveal the dynamics of the neurotransmitter sites and the fundamental link between binding and ga...
Source: Biophysical Journal - January 5, 2024 Category: Physics Authors: Anthony Auerbach Source Type: research
Phosphomimetic substitutions in TDP-43's transiently α-helical region suppress phase separation
Biophys J. 2024 Jan 4:S0006-3495(24)00001-8. doi: 10.1016/j.bpj.2024.01.001. Online ahead of print.ABSTRACTPhosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) is present within the aggregates of several age-related neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD) and Alzheimer's disease, to the point that the presence of phosphorylated TDP-43 is considered a hallmark of some of these diseases. The majority of known TDP-43 phosphorylation sites detected in ALS/FTLD patients is located in the low complexity domain (LCD), the same domain that has been sho...
Source: Biophysical Journal - January 5, 2024 Category: Physics Authors: Raza Haider Srinivasa Penumutchu Solomiia Boyko Witold K Surewicz Source Type: research
A mechanical modelling framework to study endothelial permeability
Biophys J. 2024 Jan 1:S0006-3495(23)04179-6. doi: 10.1016/j.bpj.2023.12.026. Online ahead of print.ABSTRACTThe inner lining of blood vessels, the endothelium, is made up of endothelial cells. Vascular endothelial (VE)-cadherin protein forms a bond with VE-cadherin from neighbouring cells to determine the size of gaps between the cells and thereby regulate the size of particles that can cross the endothelium. Chemical cues such as thrombin, along with mechanical properties of the cell and extracellular matrix (ECM) are known to affect the permeability of endothelial cells. Abnormal permeability is found in patients sufferin...
Source: Biophysical Journal - January 3, 2024 Category: Physics Authors: Pradeep Keshavanarayana Fabian Spill Source Type: research
Constrained dynamics of DNA oligonucleotides in phase-separated droplets
Biophys J. 2024 Jan 2:S0006-3495(23)04178-4. doi: 10.1016/j.bpj.2023.12.025. Online ahead of print.ABSTRACTUnderstanding the dynamics of biomolecules in complex environments is crucial for elucidating the effect of condensed and heterogeneous environments on their functional properties. A relevant environment - and one that can also be mimicked easily in vitro - is that of phase-separated droplets. While phase-separated droplet systems have been shown to compartmentalize a wide range of functional biomolecules, the effects of internal structuration of droplets on the dynamics and mobility of internalized molecules remain p...
Source: Biophysical Journal - January 3, 2024 Category: Physics Authors: Anupam Singh Shashi Thutupalli Manoj Kumar Sandeep Ameta Source Type: research
A mechanical modelling framework to study endothelial permeability
Biophys J. 2024 Jan 1:S0006-3495(23)04179-6. doi: 10.1016/j.bpj.2023.12.026. Online ahead of print.ABSTRACTThe inner lining of blood vessels, the endothelium, is made up of endothelial cells. Vascular endothelial (VE)-cadherin protein forms a bond with VE-cadherin from neighbouring cells to determine the size of gaps between the cells and thereby regulate the size of particles that can cross the endothelium. Chemical cues such as thrombin, along with mechanical properties of the cell and extracellular matrix (ECM) are known to affect the permeability of endothelial cells. Abnormal permeability is found in patients sufferin...
Source: Biophysical Journal - January 3, 2024 Category: Physics Authors: Pradeep Keshavanarayana Fabian Spill Source Type: research
Constrained dynamics of DNA oligonucleotides in phase-separated droplets
Biophys J. 2024 Jan 2:S0006-3495(23)04178-4. doi: 10.1016/j.bpj.2023.12.025. Online ahead of print.ABSTRACTUnderstanding the dynamics of biomolecules in complex environments is crucial for elucidating the effect of condensed and heterogeneous environments on their functional properties. A relevant environment - and one that can also be mimicked easily in vitro - is that of phase-separated droplets. While phase-separated droplet systems have been shown to compartmentalize a wide range of functional biomolecules, the effects of internal structuration of droplets on the dynamics and mobility of internalized molecules remain p...
Source: Biophysical Journal - January 3, 2024 Category: Physics Authors: Anupam Singh Shashi Thutupalli Manoj Kumar Sandeep Ameta Source Type: research
