Download MendeleyTrim-Away ubiquitinates and degrades lysine-less and N-terminally acetylated substrates.
Kiss, L., Rhinesmith, T., Luptak, J., Dickson, C.F., Weidenhausen, J., Smyly, S., Yang, J.C., Maslen, S.L., Sinning, I., Neuhaus, D., Clift, D., James, L.C.(2023) Nat Commun 14: 2160-2160
- PubMed: 37061529
- DOI: https://doi.org/10.1038/s41467-023-37504-x
- Primary Citation of Related Structures:
8A58 - PubMed Abstract:
TRIM proteins are the largest family of E3 ligases in mammals. They include the intracellular antibody receptor TRIM21, which is responsible for mediating targeted protein degradation during Trim-Away. Despite their importance, the ubiquitination mechanism of TRIM ligases has remained elusive. Here we show that while Trim-Away activation results in ubiquitination of both ligase and substrate, ligase ubiquitination is not required for substrate degradation. N-terminal TRIM21 RING ubiquitination by the E2 Ube2W can be inhibited by N-terminal acetylation, but this doesn't prevent substrate ubiquitination nor degradation. Instead, uncoupling ligase and substrate degradation prevents ligase recycling and extends functional persistence in cells. Further, Trim-Away degrades substrates irrespective of whether they contain lysines or are N-terminally acetylated, which may explain the ability of TRIM21 to counteract fast-evolving pathogens and degrade diverse substrates.
Organizational Affiliation:
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. lkiss@biochem.mpg.de.
