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• W4297999675 abstract "Abstract Biomolecular condensates, some of which are liquid-like during health, can age over time becoming gel-like pathological systems. One potential source of loss of liquid-like properties during ageing of RNA-binding protein condensates is the progressive formation of inter-protein β -sheets. To bridge microscopic understanding between accumulation of inter-protein β -sheets over time and the modulation of FUS and hnRNPA1 condensate viscoelasticity, we develop a multiscale simulation approach. Our method integrates atomistic simulations with sequence-dependent coarse-grained modelling of condensates that exhibit accumulation of inter-protein β -sheets over time. We reveal that inter-protein β -sheets notably increase condensate viscosity but does not transform the phase diagrams. Strikingly, the network of molecular connections within condensates is drastically altered, culminating in gelation when the network of strong β -sheets fully percolates. However, high concentrations of RNA decelerate the emergence of inter-protein β -sheets. Our study uncovers molecular and kinetic factors explaining how the accumulation of inter-protein β -sheets can trigger liquid-to-solid transitions in condensates, and suggests a potential mechanism to slow such transitions down." @default.
• W4297999675 created "2022-10-01" @default.
• W4297999675 creator A5006864005 @default.
• W4297999675 creator A5012231268 @default.
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• W4297999675 creator A5071393850 @default.
• W4297999675 creator A5077472156 @default.
• W4297999675 creator A5079361518 @default.
• W4297999675 date "2022-09-29" @default.
• W4297999675 modified "2023-10-14" @default.
• W4297999675 title "Protein structural transitions critically transform the network connectivity and viscoelasticity of RNA-binding protein condensates but RNA can prevent it" @default.
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