Symmetric stimulation of Hsp90 catalyzed ATP hydrolysis through enhanced active site gate dynamics.

ABSTRACT: Heat shock protein 90 (Hsp90) is a vital molecular chaperone that is essential for activating a diverse array of regulatory proteins through an ATP-dependent clamping cycle. The Hsp90 clamping cycle is driven by large-amplitude conformational changes within the N-terminal ATPase domain, including the release of an autoinhibitory N-terminal β-strap followed by a less well-characterized ATP gate rearrangement involving N-terminal helix 1. Here, we employed a combination of ¹⁹F NMR spectroscopy, molecular dynamics simulations, and ATPase assays to examine the effects of targeted β-strap and helix 1 mutations. Our findings reveal that targeted disruption of helix 1 packing against the ATPase domain accelerates clamp closure, symmetrically enhancing ATP hydrolysis for both subunits o

SUBMITTER: Magnan B 

PROVIDER: S-EPMC12205646 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature