IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-02924-7.html
   My bibliography  Save this article

UFD-2 is an adaptor-assisted E3 ligase targeting unfolded proteins

Author

Listed:
  • Doris Hellerschmied

    (Vienna BioCenter (VBC)
    Yale University)

  • Max Roessler

    (University of Vienna)

  • Anita Lehner

    (Doktor-Bohr-Gasse 3)

  • Linn Gazda

    (Vienna BioCenter (VBC))

  • Karel Stejskal

    (Vienna BioCenter (VBC))

  • Richard Imre

    (Vienna BioCenter (VBC))

  • Karl Mechtler

    (Vienna BioCenter (VBC))

  • Alexander Dammermann

    (University of Vienna)

  • Tim Clausen

    (Vienna BioCenter (VBC)
    Vienna BioCenter (VBC))

Abstract

Muscle development requires the coordinated activities of specific protein folding and degradation factors. UFD-2, a U-box ubiquitin ligase, has been reported to play a central role in this orchestra regulating the myosin chaperone UNC-45. Here, we apply an integrative in vitro and in vivo approach to delineate the substrate-targeting mechanism of UFD-2 and elucidate its distinct mechanistic features as an E3/E4 enzyme. Using Caenorhabditis elegans as model system, we demonstrate that UFD-2 is not regulating the protein levels of UNC-45 in muscle cells, but rather shows the characteristic properties of a bona fide E3 ligase involved in protein quality control. Our data demonstrate that UFD-2 preferentially targets unfolded protein segments. Moreover, the UNC-45 chaperone can serve as an adaptor protein of UFD-2 to poly-ubiquitinate unfolded myosin, pointing to a possible role of the UFD-2/UNC-45 pair in maintaining proteostasis in muscle cells.

Suggested Citation

  • Doris Hellerschmied & Max Roessler & Anita Lehner & Linn Gazda & Karel Stejskal & Richard Imre & Karl Mechtler & Alexander Dammermann & Tim Clausen, 2018. "UFD-2 is an adaptor-assisted E3 ligase targeting unfolded proteins," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02924-7
    DOI: 10.1038/s41467-018-02924-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-02924-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-02924-7?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
    ---><---

    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:9:y:2018:i:1:d:10.1038_s41467-018-02924-7. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.