Post-Translational Modification as an Allosteric Switch in Hsp90: How Dual Phosphorylation Locks Chaperone Complexes into Hyperstabilized States

Giorgio Bonollo; Benedetto Roncati; Luca Torielli; Shujuan Wang; Chiranjeevi Pasala; Silvia Pavoni; Francesco Frigerio; Fabrizio Cinquini; Gabriela Chiosis; Stefano A. Serapian; Giorgio Colombo

doi:10.1021/acs.jpclett.6c01824

July 6, 2026The Journal of Physical Chemistry LettersOpen Access

Post-Translational Modification as an Allosteric Switch in Hsp90: How Dual Phosphorylation Locks Chaperone Complexes into Hyperstabilized States

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Key Points

This research aims to explore how dual phosphorylation of Hsp90β affects its structural stability and functional interactions.
Multimicrosecond molecular dynamics simulations were conducted to analyze Hsp90β behavior under dual phosphorylation.
The study focused on the structural rigidity and allosteric changes induced by the phosphorylation at Ser226 and Ser255.
Dual phosphorylation at Ser226/Ser255 rigidifies Hsp90β, contributing to a more stable structure with an enhanced interaction capacity.
The allosteric changes propagate to distal domains, affecting cochaperone-client interfaces.
This stabilization can facilitate the formation of epichaperomes, which may have implications in disease biology.

Implication

Uncovers how dual phosphorylation stabilizes Hsp90 in disease contexts, suggesting new therapeutic targets.

Abstract

Multimicrosecond MD simulations reveal that dual phosphorylation at Ser226/Ser255 of Hsp90β acts as a molecular clamp, rigidifying the overall structure, propagating allosteric coordination changes to distal domains, and stabilizing cochaperone-client interfaces. These findings provide an atomistic mechanism by which post-translational modifications can stabilize Hsp90 interaction states that are compatible with epichaperome formation, with implications for disease biology and therapeutic targeting.

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Cite This Study

Bonollo et al. (2026) studied this question.

synapsesocial.com/papers/6a4f39a72b81a944af5746ee https://doi.org/10.1021/acs.jpclett.6c01824

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Post-Translational Modification as an Allosteric Switch in Hsp90: How Dual Phosphorylation Locks Chaperone Complexes into Hyperstabilized States

Key Points

Implication

Abstract

Discussion

Cite This Study

Post-Translational Modification as an Allosteric Switch in Hsp90: How Dual Phosphorylation Locks Chaperone Complexes into Hyperstabilized States

Key Points

Implication

Abstract

Discussion

Cite This Study

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