Journal
EMBO JOURNAL
Volume 35, Issue 11, Pages 1204-1218Publisher
WILEY
DOI: 10.15252/embj.201593741
Keywords
enzyme mechanism; protein structure; TRIM25; TRIM32; ubiquitin ligase
Categories
Funding
- Medical Research Council [U117565398]
- Francis Crick Institute from Cancer Research UK [FCI01]
- UK Medical Research Council
- Wellcome Trust
- Boehringer Ingelheim Fonds
- MRC [MC_U117533887, MC_U117565398] Funding Source: UKRI
- Medical Research Council [MC_U117533887, 1363020, MC_U117565398] Funding Source: researchfish
- The Francis Crick Institute [10029, 10178, 10142] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10015] Funding Source: researchfish
Ask authors/readers for more resources
TRIM E3 ubiquitin ligases regulate a wide variety of cellular processes and are particularly important during innate immune signalling events. They are characterized by a conserved tripartite motif in their N-terminal portion which comprises a canonical RING domain, one or two B-box domains and a coiled-coil region that mediates ligase dimerization. Self-association via the coiled-coil has been suggested to be crucial for catalytic activity of TRIMs; however, the precise molecular mechanism underlying this observation remains elusive. Here, we provide a detailed characterization of the TRIM ligases TRIM25 and TRIM32 and show how their oligomeric state is linked to catalytic activity. The crystal structure of a complex between the TRIM25 RING domain and an ubiquitin-loaded E2 identifies the structural and mechanistic features that promote a closed E2 similar to Ub conformation to activate the thioester for ubiquitin transfer allowing us to propose a model for the regulation of activity in the full-length protein. Our data reveal an unexpected diversity in the self-association mechanism of TRIMs that might be crucial for their biological function.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available