Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-21181-9
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Funding
- European Research Council (ERC) under the European Union's Seventh Framework Programme (FP7/2007-2013) through the ERC grant PhysProt [337969]
- European Research Council (ERC) under the European Union's Horizon 2020 Framework Programme through the Future and Emerging Technologies (FET) grant NanoPhlow [766972]
- European Research Council (ERC) under the Marie Sklodowska-Curie grant MicroSPARK [841466]
- European Research Council (ERC) under the Marie Sklodowska-Curie grant StressGranule [791147]
- European Research Council (ERC) under the ERC grant InsideChromatin [803326]
- Wolfson College Junior Research Fellowship
- Herchel Smith Funds
- Winton Advanced Research Fellowship
- King's College Research Fellowship
- Oppenheimer Research Fellowship
- Emmanuel College Roger Ekins Fellowship
- Polish Ministry of Science and Higher Education within the Mobilnosc Plus V fellowship [1623/MOB/V/2017/0]
- Canadian Institutes of Health Research (Foundation Grant)
- Canadian Institutes of Health Research (Canadian Consortium on Neurodegeneration in Aging Grant)
- Wellcome Trust Collaborative Award [203249/Z/16/Z]
- ALS Canada Project Grant [499553]
- ALS Society of Canada/Brain Canada [499553]
- Alzheimer's Research UK (ARUK)
- Alzheimer's Society UK
- US Alzheimer Society Zenith Grant [ZEN-18-529769]
- EPSRC Tier-2 capital grant [EP/P020259/1]
- Marie Curie Actions (MSCA) [791147, 841466] Funding Source: Marie Curie Actions (MSCA)
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The study demonstrates that cellular proteins that form condensates at low salt concentrations can reenter a phase-separated regime at high salt concentrations, driven by hydrophobic and non-ionic interactions. This sheds light on the cooperation of hydrophobic and non-ionic interactions as general driving forces in the condensation process, with implications for biomolecular condensates.
Liquid-liquid phase separation of proteins underpins the formation of membraneless compartments in living cells. Elucidating the molecular driving forces underlying protein phase transitions is therefore a key objective for understanding biological function and malfunction. Here we show that cellular proteins, which form condensates at low salt concentrations, including FUS, TDP-43, Brd4, Sox2, and Annexin A11, can reenter a phase-separated regime at high salt concentrations. By bringing together experiments and simulations, we demonstrate that this reentrant phase transition in the high-salt regime is driven by hydrophobic and non-ionic interactions, and is mechanistically distinct from the low-salt regime, where condensates are additionally stabilized by electrostatic forces. Our work thus sheds light on the cooperation of hydrophobic and non-ionic interactions as general driving forces in the condensation process, with important implications for aberrant function, druggability, and material properties of biomolecular condensates. Elucidating the molecular driving forces underlying liquid-liquid phase separation is a key objective for understanding biological function and malfunction. Here the authors show that a wide range of cellular proteins, including FUS, TDP-43, Brd4, Sox2, and Annexin A11, which form condensates at low salt concentrations, can reenter a phase-separated regime at high salt concentrations.
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