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Nat Commun. 2018 Feb 2;9(1):484. doi: 10.1038/s41467-018-02924-7.

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

Author information

1
Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030, Vienna, Austria.
2
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, 06511, USA.
3
Max F. Perutz Laboratories (MFPL), University of Vienna, Doktor-Bohr-Gasse 9, 1030, Vienna, Austria.
4
Vienna Biocenter Core Facilities, Doktor-Bohr-Gasse 3, 1030, Vienna, Austria.
5
Max F. Perutz Laboratories (MFPL), University of Vienna, Doktor-Bohr-Gasse 9, 1030, Vienna, Austria. alex.dammermann@univie.ac.at.
6
Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, 1030, Vienna, Austria. tim.clausen@imp.ac.at.
7
Medical University of Vienna, Vienna BioCenter (VBC), 1030, Vienna, Austria. tim.clausen@imp.ac.at.

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.

PMID:
29396393
PMCID:
PMC5797217
DOI:
10.1038/s41467-018-02924-7
[Indexed for MEDLINE]
Free PMC Article

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