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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
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    Cited by:

    1. Carl Elias Kutzner & Karen Carolyn Bauer & Jan-Wilm Lackmann & Richard James Acton & Anwesha Sarkar & Wojciech Pokrzywa & Thorsten Hoppe, 2024. "Optogenetic induction of mechanical muscle stress identifies myosin regulatory ubiquitin ligase NHL-1 in C. elegans," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Antonia Vogel & Renato Arnese & Ricardo M. Gudino Carrillo & Daria Sehr & Luiza Deszcz & Andrzej Bylicki & Anton Meinhart & Tim Clausen, 2024. "UNC-45 assisted myosin folding depends on a conserved FX3HY motif implicated in Freeman Sheldon Syndrome," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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