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Mühlhofer, M.* ; Peters, C.* ; Kriehuber, T.* ; Kreuzeder, M.* ; Kazman, P.* ; Rodina, N. ; Reif, B. ; Haslbeck, M.* ; Weinkauf, S.* ; Buchner, J.*

Phosphorylation activates the yeast small heat shock protein Hsp26 by weakening domain contacts in the oligomer ensemble.

Nat. Commun. 12:6697 (2021)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Hsp26 is a small heat shock protein (sHsp) from S. cerevisiae. Its chaperone activity is activated by oligomer dissociation at heat shock temperatures. Hsp26 contains 9 phosphorylation sites in different structural elements. Our analysis of phospho-mimetic mutations shows that phosphorylation activates Hsp26 at permissive temperatures. The cryo-EM structure of the Hsp26 40mer revealed contacts between the conserved core domain of Hsp26 and the so-called thermosensor domain in the N-terminal part of the protein, which are targeted by phosphorylation. Furthermore, several phosphorylation sites in the C-terminal extension, which link subunits within the oligomer, are sensitive to the introduction of negative charges. In all cases, the intrinsic inhibition of chaperone activity is relieved and the N-terminal domain becomes accessible for substrate protein binding. The weakening of domain interactions within and between subunits by phosphorylation to activate the chaperone activity in response to proteotoxic stresses independent of heat stress could be a general regulation principle of sHsps.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Alpha-b-crystallin; Chaperone Activity; Mass-spectrometry; Subunit Exchange; Global Analysis; Mechanism; Evolution; Size; Diversity; Stability
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 12, Heft: 1, Seiten: , Artikelnummer: 6697 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)
Förderungen Deutsche Forschungsgemeinschaft (German Research Foundation)