UFD-2 is an adaptor-assisted E3 ligase targeting unfolded proteins.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29396393.
- Also identified by DOI 10.1038/s41467-018-02924-7 and PMC identifier 5797217.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Caenorhabditis elegans Proteins
- Molecular Chaperones
- Muscle Cells
- Myosins
- Ubiquitin-Protein Ligase Complexes
- Ubiquitin-Protein Ligases