Open AccessRevealing the Hidden Sensitivity of Intrinsically Disordered Proteins to their Chemical Environment
Author(s) -
David Moses,
Feng Yu,
Garrett M. Ginell,
Nora M. Shamoon,
Patrick Koenig,
Alex S. Holehouse,
Shahar Sukenik
Publication year - 2020
Publication title -
the journal of physical chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.563
H-Index - 203
ISSN - 1948-7185
DOI - 10.1021/acs.jpclett.0c02822
Subject(s) - intrinsically disordered proteins , biological system , polyethylene glycol , chemical physics , characterization (materials science) , sequence (biology) , sensitivity (control systems) , polymer , chemistry , materials science , nanotechnology , biophysics , biology , biochemistry , organic chemistry , electronic engineering , engineering
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.