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bioRxiv · 10.1101/2020.12.07.414409

Sequence determinants for the aggregation and cytotoxicity of proteins within condensates generated by liquid-liquid phase separation

Vendruscolo, M.·FUXREITER, M.
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Abstract

The transition between the native and amyloid states of proteins can proceed via a deposition pathway via oligomeric intermediates or via a condensation pathway via liquid droplet intermediates generated through liquid-liquid phase separation. Here we investigate the sequence determinants of aggregation from within the droplet state based on generic interactions. We describe a model in which these sequence determinants can be captured by three features, the droplet-promoting propensity, the aggregation-promoting propensity and the binding mode entropy. By using this approach, we propose a formula to identify aggregation-promoting mutations in droplet-forming proteins. This analysis provides insights into the amino acid code for the conversion of proteins between liquid-like and solid-like condensates.

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Vendruscolo, M., FUXREITER, M.. 2020-12-07. Sequence determinants for the aggregation and cytotoxicity of proteins within condensates generated by liquid-liquid phase separation. https://doi.org/10.1101/2020.12.07.414409

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