Role of Hsp70 chaperone in client-protein folding elucidated by Markov state modeling and NMR restraint-assisted molecular dynamics simulations.

ABSTRACT: Heat shock protein 70 (Hsp70) is a molecular chaperone that plays a key role in cellular processes by assisting protein folding and preventing aggregation. During client-protein folding, Hsp70 undergoes an ATP-dependent chaperone cycle involving the opening and closing of a flexible lid. Although the open-lid and closed-lid states of Hsp70 have been studied extensively, the specific role of the lid upon its interaction with client proteins remains unclear. In this study, we generated a Markov state model from coarse-grained molecular dynamics (MD) simulations of Hsp70 spanning from open-lid to closed-lid states and sampling a flexible lid-domain conformational ensemble. Starting from metastable Hsp70 conformations with varying degrees of lid opening, we performed nuclear magnetic resonance

SUBMITTER: O'Connor MS 

PROVIDER: S-EPMC12448778 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature