PUBLICATION
Conformational dynamics modulate the catalytic activity of the molecular chaperone Hsp90
- Authors
- Mader, S.L., Lopez, A., Lawatscheck, J., Luo, Q., Rutz, D.A., Gamiz-Hernandez, A.P., Sattler, M., Buchner, J., Kaila, V.R.I.
- ID
- ZDB-PUB-200728-36
- Date
- 2020
- Source
- Nature communications 11: 1410 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Protein Binding
- Zebrafish/genetics
- Zebrafish/metabolism*
- Animals
- Models, Molecular
- Protein Conformation
- Adenosine Triphosphate/chemistry
- Adenosine Triphosphate/metabolism
- HSP90 Heat-Shock Proteins/chemistry*
- HSP90 Heat-Shock Proteins/genetics
- HSP90 Heat-Shock Proteins/metabolism*
- Protein Domains
- Hydrolysis
- Biocatalysis
- Molecular Docking Simulation
- PubMed
- 32179743 Full text @ Nat. Commun.
Citation
Mader, S.L., Lopez, A., Lawatscheck, J., Luo, Q., Rutz, D.A., Gamiz-Hernandez, A.P., Sattler, M., Buchner, J., Kaila, V.R.I. (2020) Conformational dynamics modulate the catalytic activity of the molecular chaperone Hsp90. Nature communications. 11:1410.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping