3HCT

Crystal structure of TRAF6 in complex with Ubc13 in the P1 space group

Summary for 3HCT

• Entry DOI: 10.2210/pdb3hct/pdb
• Related: 3HCS 3HCU
• Descriptor: TNF receptor-associated factor 6, Ubiquitin-conjugating enzyme E2 N, ZINC ION, ... (4 entities in total)
• Functional Keywords: cross-brace, beta-beta-alpha, coiled coil, cytoplasm, metal-binding, ubl conjugation, ubl conjugation pathway, zinc, zinc-finger, atp-binding, dna damage, dna repair, isopeptide bond, ligase, nucleotide-binding, signaling protein-ligase complex, signaling protein/ligase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : Q9Y4K3; Nucleus : P61088
• Total number of polymer chains: 2
• Total formula weight: 31412.18

Authors

Yin, Q.,Lin, S.-C.,Lamothe, B.,Lu, M.,Lo, Y.-C.,Hura, G.,Zheng, L.,Rich, R.L.,Campos, A.D.,Myszka, D.G.,Lenardo, M.J.,Darnay, B.G.,Wu, H. (deposition date: 2009-05-06, release date: 2009-05-26, Last modification date: 2023-09-06)

Primary citation

Yin, Q.,Lin, S.C.,Lamothe, B.,Lu, M.,Lo, Y.C.,Hura, G.,Zheng, L.,Rich, R.L.,Campos, A.D.,Myszka, D.G.,Lenardo, M.J.,Darnay, B.G.,Wu, H.
E2 interaction and dimerization in the crystal structure of TRAF6.
Nat.Struct.Mol.Biol., 16:658-666, 2009

PubMed Abstract: Tumor necrosis factor (TNF) receptor-associated factor (TRAF)-6 mediates Lys63-linked polyubiquitination for NF-kappaB activation via its N-terminal RING and zinc finger domains. Here we report the crystal structures of TRAF6 and its complex with the ubiquitin-conjugating enzyme (E2) Ubc13. The RING and zinc fingers of TRAF6 assume a rigid, elongated structure. Interaction of TRAF6 with Ubc13 involves direct contacts of the RING and the preceding residues, and the first zinc finger has a structural role. Unexpectedly, this region of TRAF6 is dimeric both in the crystal and in solution, different from the trimeric C-terminal TRAF domain. Structure-based mutagenesis reveals that TRAF6 dimerization is crucial for polyubiquitin synthesis and autoubiquitination. Fluorescence resonance energy transfer analysis shows that TRAF6 dimerization induces higher-order oligomerization of full-length TRAF6. The mismatch of dimeric and trimeric symmetry may provide a mode of infinite oligomerization that facilitates ligand-dependent signal transduction of many immune receptors.

PubMed: 19465916
DOI: 10.1038/nsmb.1605

Experimental method

X-RAY DIFFRACTION (2.1 Å)