RING domains act as both substrate and enzyme in a catalytic arrangement to drive self-anchored ubiquitination.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 02 2021
22 02 2021
Historique:
received:
30
09
2020
accepted:
26
01
2021
entrez:
23
2
2021
pubmed:
24
2
2021
medline:
3
3
2021
Statut:
epublish
Résumé
Attachment of ubiquitin (Ub) to proteins is one of the most abundant and versatile of all posttranslational modifications and affects outcomes in essentially all physiological processes. RING E3 ligases target E2 Ub-conjugating enzymes to the substrate, resulting in its ubiquitination. However, the mechanism by which a ubiquitin chain is formed on the substrate remains elusive. Here we demonstrate how substrate binding can induce a specific RING topology that enables self-ubiquitination. By analyzing a catalytically trapped structure showing the initiation of TRIM21 RING-anchored ubiquitin chain elongation, and in combination with a kinetic study, we illuminate the chemical mechanism of ubiquitin conjugation. Moreover, biochemical and cellular experiments show that the topology found in the structure can be induced by substrate binding. Our results provide insights into ubiquitin chain formation on a structural, biochemical and cellular level with broad implications for targeted protein degradation.
Identifiants
pubmed: 33619271
doi: 10.1038/s41467-021-21443-6
pii: 10.1038/s41467-021-21443-6
pmc: PMC7900206
doi:
Substances chimiques
Ribonucleoproteins
0
SS-A antigen
0
Ubiquitin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1220Subventions
Organisme : Medical Research Council
ID : MC_U105178934
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 200594/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U105181010
Pays : United Kingdom
Organisme : Medical Research Council
ID : U105178934
Pays : United Kingdom
Organisme : Medical Research Council
ID : U105181010
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
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