Revealing the Hidden Sensitivity of Intrinsically Disordered Proteins to Their Chemical Environment

Overview

Journal J Phys Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2020 Nov 16

PMID 33191750

Citations 37

Authors

David Moses

Feng Yu

Garrett M Ginell

Nora M Shamoon

Patrick S Koenig

Alex S Holehouse

Shahar Sukenik

Affiliations

Soon will be listed here.

Abstract

Intrinsically disordered protein-regions (IDRs) make up roughly 30% of the human proteome and are central to a wide range of biological processes. Given a lack of persistent tertiary structure, all residues in IDRs are, to some extent, solvent exposed. This extensive surface area, coupled with the absence of strong intramolecular contacts, makes IDRs inherently sensitive to their chemical environment. We report a combined experimental, computational, and analytical framework for high-throughput characterization of IDR sensitivity. Our framework reveals that IDRs can expand or compact in response to changes in their solution environment. Importantly, the direction and magnitude of conformational change depend on both protein sequence and cosolute identity. For example, some solutes such as short polyethylene glycol chains exert an expanding effect on some IDRs and a compacting effect on others. Despite this complex behavior, we can rationally interpret IDR responsiveness to solution composition changes using relatively simple polymer models. Our results imply that solution-responsive IDRs are ubiquitous and can provide an additional layer of regulation to biological systems.

Citing Articles

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