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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)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter 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)
Sprache englisch
Veröffentlichungsjahr 2022
HGF-Berichtsjahr 2022
ISSN (print) / ISBN 0021-9258
e-ISSN 1083-351X
Zeitschrift Journal of Biological Chemistry, The
Quellenangaben Band: 298, Heft: 7, Seiten: , Artikelnummer: 102101 Supplement: ,
Verlag American Society for Biochemistry and Molecular Biology
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-503000-001
Förderungen Swedish National Infrastructure for Computing
Gujarat Cancer Society
Leibniz-Rechenzentrum
Gauss Centre for Supercomputing
DOI 10.1016/j.jbc.2022.102101
WOS ID WOS:000823114600001
Scopus ID 85132861115
PubMed ID 35667441
Erfassungsdatum 2022-09-22
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