Nanoscopic Dynamics Dictate the Phase Separation Behavior of Intrinsically Disordered Proteins.

Journal Article (Journal Article)

Many intrinsically disordered proteins (IDPs) in nature may undergo liquid-liquid phase separation to assemble membraneless organelles with varied liquid-like properties and stability/dynamics. While solubility changes underlie these properties, little is known about hydration dynamics in phase-separating IDPs. Here, by studying IDP polymers of similar composition but distinct liquid-like dynamics and stability upon separation, namely, thermal hysteresis, we probe at a nanoscopic level hydration/dehydration dynamics in IDPs as they reversibly switch between phase separation states. Using continuous-wave electron paramagnetic resonance (CW EPR) spectroscopy, we observe distinct backbone and amino acid side-chain hydration dynamics in these IDPs. This nanoscopic view reveals that side-chain rehydration creates a dynamic water shield around the main-chain backbone that effectively and counterintuitively prevents water penetration and governs IDP solubility. We find that the strength of this superficial water shell is a sequence feature of IDPs that encodes for the stability of their phase-separated assemblies. Our findings expose and offer an initial understanding of how the complexity of nanoscopic water-IDP interactions dictate their rich phase separation behavior.

Full Text

Duke Authors

Cited Authors

  • Laaß, K; Quiroz, FG; Hunold, J; Roberts, S; Chilkoti, A; Hinderberger, D

Published Date

  • February 2021

Published In

Volume / Issue

  • 22 / 2

Start / End Page

  • 1015 - 1025

PubMed ID

  • 33403854

Electronic International Standard Serial Number (EISSN)

  • 1526-4602

International Standard Serial Number (ISSN)

  • 1525-7797

Digital Object Identifier (DOI)

  • 10.1021/acs.biomac.0c01768

Language

  • eng