Solutes Unmask Differences in Clustering Versus Phase Separation of FET Proteins

Overview

Journal Nat Commun

Specialty Biology

Date 2024 May 23

PMID 38782886

Authors

Mrityunjoy Kar

Laura T Vogel

Gaurav Chauhan

Suren Felekyan

Hannes Ausserwoger

Timothy J Welsh

Furqan Dar

Anjana R Kamath

Tuomas P J Knowles

Anthony A Hyman

Claus A M Seidel

Rohit V Pappu

Affiliations

Soon will be listed here.

Abstract

Phase separation and percolation contribute to phase transitions of multivalent macromolecules. Contributions of percolation are evident through the viscoelasticity of condensates and through the formation of heterogeneous distributions of nano- and mesoscale pre-percolation clusters in sub-saturated solutions. Here, we show that clusters formed in sub-saturated solutions of FET (FUS-EWSR1-TAF15) proteins are affected differently by glutamate versus chloride. These differences on the nanoscale, gleaned using a suite of methods deployed across a wide range of protein concentrations, are prevalent and can be unmasked even though the driving forces for phase separation remain unchanged in glutamate versus chloride. Strikingly, differences in anion-mediated interactions that drive clustering saturate on the micron-scale. Beyond this length scale the system separates into coexisting phases. Overall, we find that sequence-encoded interactions, mediated by solution components, make synergistic and distinct contributions to the formation of pre-percolation clusters in sub-saturated solutions, and to the driving forces for phase separation.

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