PXD025314-2

PXD025314 is an original dataset announced via ProteomeXchange.

Title	Phosphorylation activates the yeast small heat shock protein Hsp26 by weakening domain contacts in the oligomer ensemble
Description	Hsp26 is a small heat shock protein (sHsp) from S. cerevisiae. It is known to be activated by dissociation of the oligomer at heat shock temperatures. We wondered whether phosphorylation regulates its activity at physiological temperatures. In Hsp26, 9 phosphorylation sites which are located in different structural elements are known. Our analysis of phospho-mimetic mutations showed that phosphorylation activates Hsp26 at permissive temperature. 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, the C-terminal extension, which also links subunits within the oligomer, contains several phosphorylation sites. The introduction of negative charges at these strategic positions makes regions in the N-terminal domain accessible for the binding of substrate proteins. Relieving the intrinsic inhibition via different phosphorylation sites allows the fine-tuning of chaperone activity in response to proteotoxic stresses independent of heat activation. The described weakening of domain interactions within and between subunits could be a general regulation principle of sHsps.
HostingRepository	PRIDE
AnnounceDate	2021-12-17
AnnouncementXML	Submission_2021-12-17_13:47:17.491.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Moritz Mühlhofer
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-12 06:51:53	ID requested
1	2021-12-17 05:52:38	announced
⏵ 2	2021-12-17 13:47:18	announced	2021-12-17: Updated publication reference for PubMed record(s): 34795272. 2021-12-17: Updated publication reference for DOI(s): 10.1038/S41467-021-27036-7.
3	2023-11-14 08:52:09	announced	2023-11-14: Updated project metadata.

M, ü, hlhofer 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(1):6697(2021) [pubmed]

10.1038/S41467-021-27036-7;

submitter keyword: Hsp26, sHsp, phosphorylation

Johannes Buchner
contact affiliation	Center for Protein Assemblies, Department of Chemistry, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany
contact email	johannes.buchner@tum.de
lab head
Moritz Mühlhofer
contact affiliation	Dept. Chemie Lichtenbergstraße 4 85748 Garching
contact email	moritz.muehlhofer@tum.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/12/PXD025314

PRIDE project URI

• PRIDE
  1. PXD025314
     1. Label: PRIDE project
     2. Name: Phosphorylation activates the yeast small heat shock protein Hsp26 by weakening domain contacts in the oligomer ensemble