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

Moritz Mühlhofer, Carsten Peters, Thomas Kriehuber, Marina Kreuzeder, Pamina Kazman, Natalia Rodina, Bernd Reif, Martin Haslbeck, Sevil Weinkauf and Johannes Buchner ()
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Moritz Mühlhofer: Technische Universität München
Carsten Peters: Technische Universität München
Thomas Kriehuber: Technische Universität München
Marina Kreuzeder: Technische Universität München
Pamina Kazman: Technische Universität München
Natalia Rodina: Technische Universität München
Bernd Reif: Technische Universität München
Martin Haslbeck: Technische Universität München
Sevil Weinkauf: Technische Universität München
Johannes Buchner: Technische Universität München

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27036-7

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DOI: 10.1038/s41467-021-27036-7

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