Format

Send to

Choose Destination

Links from Structure

Nat Commun. 2017 Nov 27;8(1):1788. doi: 10.1038/s41467-017-01665-3.

The activity of TRAF RING homo- and heterodimers is regulated by zinc finger 1.

Author information

1
Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin, 9054, New Zealand.
2
Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin, 9054, New Zealand. catherine.day@otago.ac.nz.

Abstract

Ubiquitin chains linked through lysine63 (K63) play a critical role in inflammatory signalling. Following ligand engagement of immune receptors, the RING E3 ligase TRAF6 builds K63-linked chains together with the heterodimeric E2 enzyme Ubc13-Uev1A. Dimerisation of the TRAF6 RING domain is essential for the assembly of K63-linked ubiquitin chains. Here, we show that TRAF6 RING dimers form a catalytic complex where one RING interacts with a Ubc13~Ubiquitin conjugate, while the zinc finger 1 (ZF1) domain and linker-helix of the opposing monomer contact ubiquitin. The RING dimer interface is conserved across TRAFs and we also show that TRAF5-TRAF6 heterodimers form. Importantly, TRAF5 can provide ZF1, enabling ubiquitin transfer from a TRAF6-bound Ubc13 conjugate. Our study explains the dependence of activity on TRAF RING dimers, and suggests that both homo- and heterodimers mediated by TRAF RING domains have the capacity to synthesise ubiquitin chains.

PMID:
29176576
PMCID:
PMC5702613
DOI:
10.1038/s41467-017-01665-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center