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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)
Verlagsversion Forschungsdaten DOI
Open Access Gold
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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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter N-terminal Domain; Atp Hydrolysis; Crystal-structure; Steroid-receptor; Proton-transfer; Binding-site; Mechanism; Protein; Cycle; System
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 11, Heft: 1, Seiten: , Artikelnummer: 1410 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed