Electrostatic Collapse of Intrinsically Disordered Acid-Rich Protein Is Sensitive to Counterion Valency.

ABSTRACT: Intrinsically disordered proteins (IDPs) respond sensitively to their ionic environment, yet the mechanisms driving ion-induced conformational changes remain incompletely understood. Here, we investigate how counterion valency modulates the dimensions of an extremely charged model IDP, the aspartic and glutamic acid-rich protein AGARP. Fluorescence correlation spectroscopy and size exclusion chromatography reveal a pronounced, valency-dependent reduction in its hydrodynamic radius, with divalent cations (Ca²⁺, Mg²⁺) inducing collapse at much lower activities than monovalent cations (Na⁺, K⁺). Molecular dynamics simulations, direct sampling, and polyampholyte theory quantitatively capture the Debye-Hückel screening by monovalent ions but not the e

SUBMITTER: Klepka BP 

PROVIDER: S-EPMC12557392 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature