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

Phase separation of multicomponent peptide mixtures into dehydrated clusters with hydrophilic cores
Biophys J. 2024 Jan 1:S0006-3495(23)04180-2. doi: 10.1016/j.bpj.2023.12.027. Online ahead of print.ABSTRACTPhase separation of biomolecules underlies the formation and regulation of various membraneless condensates in cells. How condensates function reliably while surrounded by heterogeneous and dynamic mixtures of biomolecular components with specific and non-specific interactions is yet to be understood. Studying multi-component biomolecular mixtures with designer peptides has recently become an attractive avenue for learning about physicochemical principles governing cellular condensates. In this work, we employed long ...
Source: Biophysical Journal - January 2, 2024 Category: Physics Authors: W Brown D A Potoyan Source Type: research

Phase separation of multicomponent peptide mixtures into dehydrated clusters with hydrophilic cores
Biophys J. 2024 Jan 1:S0006-3495(23)04180-2. doi: 10.1016/j.bpj.2023.12.027. Online ahead of print.ABSTRACTPhase separation of biomolecules underlies the formation and regulation of various membraneless condensates in cells. How condensates function reliably while surrounded by heterogeneous and dynamic mixtures of biomolecular components with specific and non-specific interactions is yet to be understood. Studying multi-component biomolecular mixtures with designer peptides has recently become an attractive avenue for learning about physicochemical principles governing cellular condensates. In this work, we employed long ...
Source: Biophysical Journal - January 2, 2024 Category: Physics Authors: W Brown D A Potoyan Source Type: research

Bound ions effects: Using machine learning method to study the kinesin Ncd binding with microtubule
Biophys J. 2023 Dec 29:S0006-3495(23)04176-0. doi: 10.1016/j.bpj.2023.12.024. Online ahead of print.ABSTRACTDrosophila Ncd proteins are motor proteins that play important roles in spindle organization. The Ncd and tubulin dimer are highly charged. Thus, it is crucial to investigate Ncd-tubulin dimer interactions in the presence of ions, especially ions that are bound or restricted at the Ncd-tubulin dimer binding interfaces. To consider the ion effects, the widely used implicit solvent models treat ions implicitly in the continuous solvent environment, without focusing on the individual ions' effects. But the highly charge...
Source: Biophysical Journal - December 31, 2023 Category: Physics Authors: Wenhan Guo Dan Du Houfang Zhang Jason E Sanchez Shengjie Sun Wang Xu Yunhui Peng Lin Li Source Type: research

Coupling Liquid Phases in 3D Condensates and 2D Membranes: Successes, Challenges, and Tools
Biophys J. 2023 Dec 29:S0006-3495(23)04177-2. doi: 10.1016/j.bpj.2023.12.023. Online ahead of print.ABSTRACTThis review describes the major experimental challenges researchers meet when attempting to couple phase separation between membranes and condensates. Although it is well known that phase separation in a 2D membrane should affect molecules capable of forming a 3D condensate (and vice versa), few researchers have quantified the effects to date. The scarcity of these measurements is not due to lack of intense interest or effort in the field. Rather, it reflects significant experimental challenges in manipulating couple...
Source: Biophysical Journal - December 31, 2023 Category: Physics Authors: Heidi M J Weakly Sarah L Keller Source Type: research

Efficient Enumeration and Visualization of Helix-Coil Ensembles
We present an algorithm that efficiently approximates the helix-coil ensemble to arbitrary accuracy, by sequentially generating a list of the M highest populated configurations in descending order of population. Truncating this list of (configuration, population) pairs at a desired accuracy provides an approximating sub-ensemble. We demonstrate several uses of this approach for providing insight into helix-coil ensembles and folding mechanisms, including landscape visualization.PMID:38158653 | DOI:10.1016/j.bpj.2023.12.021 (Source: Biophysical Journal)
Source: Biophysical Journal - December 30, 2023 Category: Physics Authors: Roy G Hughes Shiwen Zhao Terrence G Oas Scott C Schmidler Source Type: research

Non-additivity in interactions between three membrane-wrapped colloidal spheres
Biophys J. 2023 Dec 28:S0006-3495(23)04158-9. doi: 10.1016/j.bpj.2023.12.020. Online ahead of print.ABSTRACTMany cell functions require a concerted effort from multiple membrane proteins, for example, for signaling, cell division, and endocytosis. One contribution to their successful self-organization stems from the membrane deformations that these proteins induce. While the pairwise interaction potential of two membrane deforming spheres has recently been measured, membrane-deformation induced interactions have been predicted to be non-additive and hence their collective behavior cannot be deduced from this measurement. W...
Source: Biophysical Journal - December 30, 2023 Category: Physics Authors: Ali Azadbakht Billie Meadowcroft Juraj M ájek An đela Šarić Daniela J Kraft Source Type: research

Unmasking subtype-dependent susceptibility to C-type inactivation in mammalian Kv1 channels
In this study, we report alternative ways to measure or elicit conformational changes in the outer pore associated with C-type inactivation. Using a strategically substituted cysteine in the outer pore, we demonstrate that mutation of Kv1.2 V381 (equivalent to Shaker T449) or W366 (Shaker W434) markedly increases susceptibility to modification by extracellularly applied MTSET. Moreover, due to the cooperative nature of C-type inactivation, Kv1.2 assembly in heteromeric channels markedly inhibits MTSET modification of this substituted cysteine in neighboring subunits. The identity of Kv1.2 residue V381 also markedly influen...
Source: Biophysical Journal - December 29, 2023 Category: Physics Authors: Victoria A Baronas Anson Wong Damayantee Das Shawn M Lamothe Harley T Kurata Source Type: research

Unmasking subtype-dependent susceptibility to C-type inactivation in mammalian Kv1 channels
In this study, we report alternative ways to measure or elicit conformational changes in the outer pore associated with C-type inactivation. Using a strategically substituted cysteine in the outer pore, we demonstrate that mutation of Kv1.2 V381 (equivalent to Shaker T449) or W366 (Shaker W434) markedly increases susceptibility to modification by extracellularly applied MTSET. Moreover, due to the cooperative nature of C-type inactivation, Kv1.2 assembly in heteromeric channels markedly inhibits MTSET modification of this substituted cysteine in neighboring subunits. The identity of Kv1.2 residue V381 also markedly influen...
Source: Biophysical Journal - December 29, 2023 Category: Physics Authors: Victoria A Baronas Anson Wong Damayantee Das Shawn M Lamothe Harley T Kurata Source Type: research

Unmasking subtype-dependent susceptibility to C-type inactivation in mammalian Kv1 channels
In this study, we report alternative ways to measure or elicit conformational changes in the outer pore associated with C-type inactivation. Using a strategically substituted cysteine in the outer pore, we demonstrate that mutation of Kv1.2 V381 (equivalent to Shaker T449) or W366 (Shaker W434) markedly increases susceptibility to modification by extracellularly applied MTSET. Moreover, due to the cooperative nature of C-type inactivation, Kv1.2 assembly in heteromeric channels markedly inhibits MTSET modification of this substituted cysteine in neighboring subunits. The identity of Kv1.2 residue V381 also markedly influen...
Source: Biophysical Journal - December 29, 2023 Category: Physics Authors: Victoria A Baronas Anson Wong Damayantee Das Shawn M Lamothe Harley T Kurata Source Type: research

Unmasking subtype-dependent susceptibility to C-type inactivation in mammalian Kv1 channels
In this study, we report alternative ways to measure or elicit conformational changes in the outer pore associated with C-type inactivation. Using a strategically substituted cysteine in the outer pore, we demonstrate that mutation of Kv1.2 V381 (equivalent to Shaker T449) or W366 (Shaker W434) markedly increases susceptibility to modification by extracellularly applied MTSET. Moreover, due to the cooperative nature of C-type inactivation, Kv1.2 assembly in heteromeric channels markedly inhibits MTSET modification of this substituted cysteine in neighboring subunits. The identity of Kv1.2 residue V381 also markedly influen...
Source: Biophysical Journal - December 29, 2023 Category: Physics Authors: Victoria A Baronas Anson Wong Damayantee Das Shawn M Lamothe Harley T Kurata Source Type: research

Binding-Induced Lipid Domains: Peptide-Membrane Interactions with PIP < sub > 2 < /sub > and PS
Biophys J. 2023 Dec 22:S0006-3495(23)04157-7. doi: 10.1016/j.bpj.2023.12.019. Online ahead of print.ABSTRACTCell signaling is an important process involving complex interactions between lipids and proteins. The myristoylated alanine-rich C-kinase substrate (MARCKS) has been established as a key signaling regulator, serving a range of biological roles. Its effector domain (ED), which anchors the protein to the plasma membrane, induces domain formation in membranes containing phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylserine (PS). The mechanisms governing the MARCKS-ED binding to membranes remain elusive. H...
Source: Biophysical Journal - December 24, 2023 Category: Physics Authors: Ziareena A Al-Mualem Xiaobing Chen Azam Shafieenezhad Eric N Senning Carlos R Baiz Source Type: research

Binding-Induced Lipid Domains: Peptide-Membrane Interactions with PIP < sub > 2 < /sub > and PS
Biophys J. 2023 Dec 22:S0006-3495(23)04157-7. doi: 10.1016/j.bpj.2023.12.019. Online ahead of print.ABSTRACTCell signaling is an important process involving complex interactions between lipids and proteins. The myristoylated alanine-rich C-kinase substrate (MARCKS) has been established as a key signaling regulator, serving a range of biological roles. Its effector domain (ED), which anchors the protein to the plasma membrane, induces domain formation in membranes containing phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylserine (PS). The mechanisms governing the MARCKS-ED binding to membranes remain elusive. H...
Source: Biophysical Journal - December 24, 2023 Category: Physics Authors: Ziareena A Al-Mualem Xiaobing Chen Azam Shafieenezhad Eric N Senning Carlos R Baiz Source Type: research

Binding-Induced Lipid Domains: Peptide-Membrane Interactions with PIP < sub > 2 < /sub > and PS
Biophys J. 2023 Dec 22:S0006-3495(23)04157-7. doi: 10.1016/j.bpj.2023.12.019. Online ahead of print.ABSTRACTCell signaling is an important process involving complex interactions between lipids and proteins. The myristoylated alanine-rich C-kinase substrate (MARCKS) has been established as a key signaling regulator, serving a range of biological roles. Its effector domain (ED), which anchors the protein to the plasma membrane, induces domain formation in membranes containing phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylserine (PS). The mechanisms governing the MARCKS-ED binding to membranes remain elusive. H...
Source: Biophysical Journal - December 24, 2023 Category: Physics Authors: Ziareena A Al-Mualem Xiaobing Chen Azam Shafieenezhad Eric N Senning Carlos R Baiz Source Type: research

Binding-Induced Lipid Domains: Peptide-Membrane Interactions with PIP < sub > 2 < /sub > and PS
Biophys J. 2023 Dec 22:S0006-3495(23)04157-7. doi: 10.1016/j.bpj.2023.12.019. Online ahead of print.ABSTRACTCell signaling is an important process involving complex interactions between lipids and proteins. The myristoylated alanine-rich C-kinase substrate (MARCKS) has been established as a key signaling regulator, serving a range of biological roles. Its effector domain (ED), which anchors the protein to the plasma membrane, induces domain formation in membranes containing phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylserine (PS). The mechanisms governing the MARCKS-ED binding to membranes remain elusive. H...
Source: Biophysical Journal - December 24, 2023 Category: Physics Authors: Ziareena A Al-Mualem Xiaobing Chen Azam Shafieenezhad Eric N Senning Carlos R Baiz Source Type: research