: 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.
Post-Translational Modification as an Allosteric Switch in Hsp90: How Dual Phosphorylation Locks Chaperone Complexes into Hyperstabilized States
Bonollo, Giorgio;Torielli, Luca;Serapian, Stefano A.;Colombo, Giorgio
2026-01-01
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.File in questo prodotto:
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