IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-27036-7.html
   My bibliography  Save this article

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

Author

Listed:
  • Moritz Mühlhofer

    (Technische Universität München)

  • Carsten Peters

    (Technische Universität München)

  • Thomas Kriehuber

    (Technische Universität München
    Boehringer Ingelheim)

  • Marina Kreuzeder

    (Technische Universität München
    Ludwig-Maximilians-Universität München)

  • Pamina Kazman

    (Technische Universität München
    Roche Diagnostics)

  • Natalia Rodina

    (Technische Universität München
    Deutsches Forschungszentrum für Gesundheit und Umwelt)

  • Bernd Reif

    (Technische Universität München
    Deutsches Forschungszentrum für Gesundheit und Umwelt)

  • Martin Haslbeck

    (Technische Universität München)

  • Sevil Weinkauf

    (Technische Universität München)

  • Johannes Buchner

    (Technische Universität München)

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.

Suggested Citation

  • Moritz Mühlhofer & Carsten Peters & Thomas Kriehuber & Marina Kreuzeder & Pamina Kazman & Natalia Rodina & Bernd Reif & Martin Haslbeck & Sevil Weinkauf & Johannes Buchner, 2021. "Phosphorylation activates the yeast small heat shock protein Hsp26 by weakening domain contacts in the oligomer ensemble," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27036-7
    DOI: 10.1038/s41467-021-27036-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-27036-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-27036-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Kyeong Kyu Kim & Rosalind Kim & Sung-Hou Kim, 1998. "Crystal structure of a small heat-shock protein," Nature, Nature, vol. 394(6693), pages 595-599, August.
    2. Sophia Ungelenk & Fatemeh Moayed & Chi-Ting Ho & Tomas Grousl & Annette Scharf & Alireza Mashaghi & Sander Tans & Matthias P. Mayer & Axel Mogk & Bernd Bukau, 2016. "Small heat shock proteins sequester misfolding proteins in near-native conformation for cellular protection and efficient refolding," Nature Communications, Nature, vol. 7(1), pages 1-14, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Kevin Wu & Thomas C. Minshull & Sheena E. Radford & Antonio N. Calabrese & James C. A. Bardwell, 2022. "Trigger factor both holds and folds its client proteins," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Y Hoang & Christopher A. Azaldegui & Rachel E. Dow & Maria Ghalmi & Julie S. Biteen & Anthony G. Vecchiarelli, 2024. "An experimental framework to assess biomolecular condensates in bacteria," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27036-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.