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Mader, S.L.* ; Lopez, A. ; Lawatscheck, J.* ; Luo, Q.* ; Rutz, D.A.* ; Gamiz-Hernandez, A.P.* ; Sattler, M. ; Buchner, J.* ; Kaila, V.R.I.*

Conformational dynamics modulate the catalytic activity of the molecular chaperone Hsp90.

Nat. Commun. 11:1410 (2020)
Publ. Version/Full Text Research data DOI PMC
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords N-terminal Domain; Atp Hydrolysis; Crystal-structure; Steroid-receptor; Proton-transfer; Binding-site; Mechanism; Protein; Cycle; System
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 11, Issue: 1, Pages: , Article Number: 1410 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Structural Biology (STB)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503000-001
DOI 10.1038/s41467-020-15050-0
WOS ID WOS:000521328300011
Scopus ID 85081989033
PubMed ID 32179743
Erfassungsdatum 2020-05-13
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