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Biebl, M.M.* ; Lopez, A. ; Rehn, A.* ; Freiburger, L.* ; Lawatscheck, J.* ; Blank, B.* ; Sattler, M. ; Buchner, J.*

Structural elements in the flexible tail of the co-chaperone p23 coordinate client binding and progression of the Hsp90 chaperone cycle.

Nat. Commun. 12:828 (2021)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
The co-chaperone p23 is a central part of the Hsp90 machinery. It stabilizes the closed conformation of Hsp90, inhibits its ATPase and is important for client maturation. Yet, how this is achieved has remained enigmatic. Here, we show that a tryptophan residue in the proximal region of the tail decelerates the ATPase by allosterically switching the conformation of the catalytic loop in Hsp90. We further show by NMR spectroscopy that the tail interacts with the Hsp90 client binding site via a conserved helix. This helical motif in the p23 tail also binds to the client protein glucocorticoid receptor (GR) in the free and Hsp90-bound form. In vivo experiments confirm the physiological importance of ATPase modulation and the role of the evolutionary conserved helical motif for GR activation in the cellular context.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 12, Heft: 1, Seiten: , Artikelnummer: 828 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Förderungen DFG via Center for Integrated Protein Science Munich (CIPSM)
Fonds der Chemischen Industrie
SFB1035 (German Research Foundation DFG)