Conformational dynamics modulate the catalytic activity of the molecular chaperone Hsp90.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 03 2020
16 03 2020
Historique:
received:
26
12
2018
accepted:
16
02
2020
entrez:
18
3
2020
pubmed:
18
3
2020
medline:
28
7
2020
Statut:
epublish
Résumé
The heat shock protein 90 (Hsp90) is a molecular chaperone that employs the free energy of ATP hydrolysis to control the folding and activation of several client proteins in the eukaryotic cell. To elucidate how the local ATPase reaction in the active site couples to the global conformational dynamics of Hsp90, we integrate here large-scale molecular simulations with biophysical experiments. We show that the conformational switching of conserved ion pairs between the N-terminal domain, harbouring the active site, and the middle domain strongly modulates the catalytic barrier of the ATP-hydrolysis reaction by electrostatic forces. Our combined findings provide a mechanistic model for the coupling between catalysis and protein dynamics in Hsp90, and show how long-range coupling effects can modulate enzymatic activity.
Identifiants
pubmed: 32179743
doi: 10.1038/s41467-020-15050-0
pii: 10.1038/s41467-020-15050-0
pmc: PMC7075974
doi:
Substances chimiques
HSP90 Heat-Shock Proteins
0
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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