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Zierer, B.K.* ; Rübbelke, M. ; Tippel, F.* ; Madl, T. ; Schopf, F.H.* ; Rutz, D.A.* ; Richter, K.* ; Sattler, M. ; Buchner, J.*

Importance of cycle timing for the function of the molecular chaperone Hsp90.

Nat. Struct. Mol. Biol. 23, 1020-1028 (2016)
Verlagsversion Postprint Forschungsdaten DOI
Open Access Gold
Hsp90 couples ATP hydrolysis to large conformational changes essential for activation of client proteins. The structural transitions involve dimerization of the N-terminal domains and formation of 'closed states' involving the N-terminal and middle domains. Here, we used Hsp90 mutants that modulate ATPase activity and biological function as probes to address the importance of conformational cycling for Hsp90 activity. We found no correlation between the speed of ATP turnover and the in vivo activity of Hsp90: some mutants with almost normal ATPase activity were lethal, and some mutants with lower or undetectable ATPase activity were viable. Our analysis showed that it is crucial for Hsp90 to attain and spend time in certain conformational states: a certain dwell time in open states is required for optimal processing of client proteins, whereas a prolonged population of closed states has negative effects. Thus, the timing of conformational transitions is crucial for Hsp90 function and not cycle speed.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Heat-shock-protein; Escherichia-coli Hsp90; Atp Hydrolysis; In-vivo; Steroid-receptor; Client Protein; Mechanism; Nucleotide; Binding; Kinase
Sprache
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 1545-9993
e-ISSN 1545-9985
Zeitschrift Nature Structural & Molecular Biology
Quellenangaben Band: 23, Heft: 11, Seiten: 1020-1028 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)
POF Topic(s) 30505 - New Technologies for Biomedical Discoveries
30203 - Molecular Targets and Therapies
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-552800-001
G-503000-001
DOI 10.1038/nsmb.3305
WOS ID WOS:000386992700013
Erfassungsdatum 2016-11-24
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