5VO0

Structure of a TRAF6-Ubc13~Ub complex

Summary for 5VO0

• Entry DOI: 10.2210/pdb5vo0/pdb
• Related: 5VNZ
• Descriptor: TNF receptor-associated factor 6, Ubiquitin-conjugating enzyme E2 N, Ubiquitin, ... (5 entities in total)
• Functional Keywords: transferase
• Biological source: Danio rerio (Zebrafish); More
• Cellular location: Nucleus : P61088; Ubiquitin: Cytoplasm : P0CG47
• Total number of polymer chains: 6
• Total formula weight: 92379.40

Authors

Middleton, A.J.,Day, C.L. (deposition date: 2017-05-01, release date: 2017-12-06, Last modification date: 2024-10-09)

Primary citation

Middleton, A.J.,Budhidarmo, R.,Das, A.,Zhu, J.,Foglizzo, M.,Mace, P.D.,Day, C.L.
The activity of TRAF RING homo- and heterodimers is regulated by zinc finger 1.
Nat Commun, 8:1788-1788, 2017

PubMed 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.

PubMed: 29176576
DOI: 10.1038/s41467-017-01665-3

Experimental method

X-RAY DIFFRACTION (3.9 Å)