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Jussupow, A.* ; Lopez, A. ; Baumgart, M.* ; Mader, S.L.* ; Sattler, M. ; Kaila, V.R.I.*

Extended conformational states dominate the Hsp90 chaperone dynamics.

J. Biol. Chem. 298:102101 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
The heat shock protein 90 (Hsp90) is a molecular chaperone central to client protein folding and maturation in eukaryotic cells. During its chaperone cycle, Hsp90 undergoes ATPase-coupled large-scale conformational changes between open and closed states, where the N-terminal and middle domains of the protein form a compact dimerized conformation. However, the molecular principles of the switching motion between the open and closed states remain poorly understood. Here we show by integrating atomistic and coarse-grained molecular simulations with small-angle X-ray scattering experiments and nuclear magnetic resonance spectroscopy data that Hsp90 exhibits rich conformational dynamics modulated by the charged linker, which connects the N-terminal with the middle domain of the protein. We show that the dissociation of these domains is crucial for the conformational flexibility of the open state, with the separation distance controlled by a beta-sheet motif next to the linker region. Taken together, our results suggest that the conformational ensemble of Hsp90 comprises highly extended states, which could be functionally crucial for client processing.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Md Simulations ; Chaperone ; Coarse-grained Simulation ; Heat Shock Protein (hsp) ; Heat Shock Protein 90 (hsp90) ; Molecular Dynamics ; Nuclear Magnetic Resonance (nmr) ; Small‐angle X‐ray Scattering (saxs)
ISSN (print) / ISBN 0021-9258
e-ISSN 1083-351X
Journal Journal of Biological Chemistry, The
Quellenangaben Volume: 298, Issue: 7, Pages: , Article Number: 102101 Supplement: ,
Publisher American Society for Biochemistry and Molecular Biology
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Structural Biology (STB)
Grants Swedish National Infrastructure for Computing
Gujarat Cancer Society
Leibniz-Rechenzentrum
Gauss Centre for Supercomputing