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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / metabolism*
  • Molecular Chaperones / metabolism*
  • Muscle Cells / metabolism*
  • Myosins / metabolism*
  • Proteostasis
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligase Complexes / metabolism*
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination
  • Unfolded Protein Response


  • Caenorhabditis elegans Proteins
  • Molecular Chaperones
  • Ubiquitin
  • unc-45 protein, C elegans
  • Ubiquitin-Protein Ligase Complexes
  • Ubiquitin-Protein Ligases
  • Myosins
  • ufd-2 protein, C elegans