Direct and indirect salt effects on homotypic phase separation DOI Creative Commons

Matt MacAinsh,

Souvik Dey, Huan‐Xiang Zhou

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Nov. 12, 2024

The low-complexity domain of hnRNPA1 (A1-LCD) phase separates in a salt-dependent manner. Unlike many intrinsically disordered proteins (IDPs) whose separation is suppressed by increasing salt concentrations, the A1-LCD promoted >100 mM NaCl. To investigate atypical effect on separation, we carried out all-atom molecular dynamics simulations systems comprising multiple chains at NaCl concentrations from 50 to 1000 ions occupy first shell as well more distant sites around IDP chains, with Arg sidechains and backbone carbonyls favored partners Cl – Na + , respectively. They play two direct roles driving condensation. neutralize high net charge protein (+9) an excess bound over ; second bridge between thereby fortifying intermolecular interaction networks dense phase. At also indirectly strengthens π–π, cation–π, amino–π interactions, drawing water away partners. Therefore, low salt, prevented repulsion; intermediate neutralizes enough while bridging drive separation. This becomes even stronger due strengthened π-type interactions. Based this understanding, four classes dependence can be predicted amino-acid composition.

Language: Английский

神经退行性疾病相关淀粉样蛋白的液-液相分离 DOI

Yun-Yi Luo,

Yanmei Li

Chinese Science Bulletin (Chinese Version), Journal Year: 2025, Volume and Issue: 70(7), P. 850 - 859

Published: Feb. 12, 2025

Citations

1
Aging-dependent evolving electrochemical potentials of biomolecular condensates regulate their physicochemical activities DOI
Wen Yu,

Xiao Guo,

Yu Xia

et al.

Nature Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Language: Английский

Citations

1
pH-Responsive Phase Separation Dynamics of Intrinsically Disordered Peptides DOI Creative Commons
Manali Nandy, Ketan A. Ganar, Hans Ippel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

Abstract Liquid-liquid phase separation of biomolecules is crucial for maintaining the functional organization in biological systems. Intrinsically disordered proteins are particularly prone to form phase-separated condensates response various physicochemical triggers. While effect ionic strength and temperature on dynamics have been studied extensively, influence pH less explored. Here, we study a model glycine-rich protein present tick bioadhesive, given its capability undergo separation. After confirming nature through spectroscopy, investigated dependence underlying molecular mechanisms. Our findings reveal that significantly influences hydrophobicity via residues, driving notable variations coacervation behavior (propensity, progression) shaping material properties (viscosity, interfacial activity) formed condensates. Given ubiquitous presence biology, this provides valuable insights about broad implications pH-dependent intrinsically proteins.

Language: Английский

Citations

0
Context Dependency of Hydrophobicity in Intrinsically Disordered Proteins: Insights from a New Dewetting Free Energy-Based Hydrophobicity Scale DOI Creative Commons
Saeed Najafi,

Samuel Lobo,

M. Scott Shell

et al.

The Journal of Physical Chemistry B, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

The interaction between amino acids (AAs) and hydration water is fundamental to protein folding protein–protein interactions. Here, we proposed a hydrophobicity scale for AAs based on their computed free energetic cost of dewetting. This metric captures both entropic enthalpic contributions AA–water interactions allows systematic intuitive classification AAs. Using indirect umbrella sampling (INDUS), rank individual the relative magnitude dewetting energies, from lowest (most hydrophobic) highest hydrophilic). new starting point evaluate different elements behavior, focus here structure translational diffusivity waters. While latter commonly used as proxy hydrophobicity, show that its behavior in fact nonmonotonic: hydrophobic residues slow diffusion due highly structured networks, while hydrophilic have strong hydrogen bonds with despite less networks. We extend our analysis properties intrinsically disordered peptides varied sequence patterning (sequences proline/leucine arginine/glutamic acid residues). find these context-dependent, (hydrophilic) patches cooperatively enhancing (hydrophilicity). These molecular insights sequence-dependent behaviors may be particularly impactful study proteins implicated liquid–liquid phase separation aggregation, processes where AAs' environments are complex changing.

Language: Английский

Citations

0
Protein modifications and ionic strength show the difference between protein-mediated and solvent-mediated regulation of biomolecular condensation DOI Creative Commons

A. Czajkowski,

Abhirami Udayabanu,

Manthan Raj

et al.

Frontiers in Nanotechnology, Journal Year: 2025, Volume and Issue: 7

Published: March 5, 2025

Biomolecular condensation is an important mechanism of cellular compartmentalization without membranes. Formation liquid-like condensates biomolecules involves protein-protein interactions working in tandem with protein-water interactions. The balance these condensate-forming proteins impacted by multiple factors inside a living organism. This work investigates the effects post-translational modifications (PTMs) and salt concentration as two such perturbing on protein Fused Sarcoma (FUS), RNA binding protein. was obtained from expression systems differing their capability to add PTMs protein, bacterial insect cell. Attenuated total reflection Terahertz spectroscopy used probe solvation behavior formed FUS at 100 mM 2.5 M KCl. results show that while impact phase-separating propensity, they do not alter condensate. On other hand, found stiffness water hydrogen bond network. These findings have implications for biomolecular chemistry, showing condensate molecular organization perturbed fluctuations solvent properties.

Language: Английский

Citations

0
Adsorption of ciprofloxacin on (Zn-Al) LDHs modified 3D reduced graphene oxide:Response surface methodology, adsorption equilibrium, kinetic and thermodynamic studies DOI

Chong Lu,

Xing-Wei Han,

Haojun Zou

et al.

Chinese Journal of Chemical Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Raman spectroscopy and imaging of protein droplet formation and aggregation DOI
Matthew D. Watson, Jennifer C. Lee

Current Opinion in Structural Biology, Journal Year: 2025, Volume and Issue: 92, P. 103041 - 103041

Published: April 3, 2025

Language: Английский

Citations

0
Direct and indirect salt effects on homotypic phase separation DOI Creative Commons

Matt MacAinsh,

Souvik Dey, Huan‐Xiang Zhou

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Aug. 12, 2024

The low-complexity domain of hnRNPA1 (A1-LCD) phase separates in a salt-dependent manner. Unlike many intrinsically disordered proteins (IDPs) whose separation is suppressed by increasing salt concentrations, the A1-LCD promoted >100 mM NaCl. To investigate atypical effect on separation, we carried out all-atom molecular dynamics simulations systems comprising multiple chains at NaCl concentrations from 50 to 1000 ions occupy first shell as well more distant sites around IDP chains, with Arg sidechains and backbone carbonyls favored partners Cl – Na + , respectively. They play two direct roles driving condensation. neutralize high net charge protein (+9) an excess bound over ; second bridge between thereby fortifying intermolecular interaction networks dense phase. At also indirectly strengthens π–π, cation–π, amino–π interactions, drawing water away partners. Therefore, low salt, prevented repulsion; intermediate neutralizes enough while bridging drive separation. This becomes even stronger due strengthened π-type interactions. Based this understanding, four classes dependence can be predicted amino-acid composition.

Language: Английский

Citations

2
Direct and Indirect Salt Effects on Homotypic Phase Separation DOI Open Access

Matthew MacAinsh,

Souvik Dey, Huan‐Xiang Zhou

et al.

Published: Oct. 21, 2024

The low-complexity domain of hnRNPA1 (A1-LCD) phase separates in a salt-dependent manner. Unlike many intrinsically disordered proteins (IDPs) whose separation is suppressed by increasing salt concentrations, the A1-LCD promoted > 100 mM NaCl. To investigate atypical effect on separation, we carried out all-atom molecular dynamics simulations systems comprising multiple chains at NaCl concentrations from 50 to 1000 ions occupy first-shell as well more distant sites around IDP chains, with Arg sidechains and backbone carbonyls favored partners Cl − Na + , respectively. They play two direct roles driving condensation. first neutralize high net charge protein (+9) an excess bound over ; second bridge between thereby fortifying intermolecular interaction networks dense phase. At also indirectly strengthens π-π, cation-π, amino-π interactions, drawing water away partners. Therefore, low salt, prevented repulsion; intermediate neutralizes enough while bridging drive separation. This becomes even stronger due strengthened π-type interactions. Based this understanding, four classes dependence can be predicted amino-acid composition.

Language: Английский

Citations

1
Direct and indirect salt effects on homotypic phase separation DOI Creative Commons

Matt MacAinsh,

Souvik Dey, Huan‐Xiang Zhou

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Nov. 12, 2024

The low-complexity domain of hnRNPA1 (A1-LCD) phase separates in a salt-dependent manner. Unlike many intrinsically disordered proteins (IDPs) whose separation is suppressed by increasing salt concentrations, the A1-LCD promoted >100 mM NaCl. To investigate atypical effect on separation, we carried out all-atom molecular dynamics simulations systems comprising multiple chains at NaCl concentrations from 50 to 1000 ions occupy first shell as well more distant sites around IDP chains, with Arg sidechains and backbone carbonyls favored partners Cl – Na + , respectively. They play two direct roles driving condensation. neutralize high net charge protein (+9) an excess bound over ; second bridge between thereby fortifying intermolecular interaction networks dense phase. At also indirectly strengthens π–π, cation–π, amino–π interactions, drawing water away partners. Therefore, low salt, prevented repulsion; intermediate neutralizes enough while bridging drive separation. This becomes even stronger due strengthened π-type interactions. Based this understanding, four classes dependence can be predicted amino-acid composition.

Language: Английский

Citations

1