8A58

X-ray structure of TRIM21 RING E3 ligase in complex with E2 enzyme Ube2W

Summary for 8A58

• Entry DOI: 10.2210/pdb8a58/pdb
• Descriptor: Ubiquitin-conjugating enzyme E2 W, E3 ubiquitin-protein ligase TRIM21, ZINC ION, ... (4 entities in total)
• Functional Keywords: e3 ubiquitin ligase, ligase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 54514.20

Authors

James, L.C.,Kiss, L. (deposition date: 2022-06-14, release date: 2023-04-26, Last modification date: 2024-02-07)

Primary citation

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.
Trim-Away ubiquitinates and degrades lysine-less and N-terminally acetylated substrates.
Nat Commun, 14:2160-2160, 2023

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.

PubMed: 37061529
DOI: 10.1038/s41467-023-37504-x

Experimental method

X-RAY DIFFRACTION (2.25 Å)