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Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions

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Espinosa, Jorge R. 


Abstract: 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.


Funder: See Main Article file (Acknowledgments section).


Article, /631/45/612, /631/57, /631/57/2269, /639/638/440/56, /639/766/747, /9, /14/35, /119, /14/63, /82/83, /132, /119/118, article

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Nature Communications

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Nature Publishing Group UK