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Nat Struct Mol Biol. 2009 Jun;16(6):658-66. doi: 10.1038/nsmb.1605. Epub 2009 May 24.

E2 interaction and dimerization in the crystal structure of TRAF6.

Author information

1
Weill Medical College of Cornell University, New York, New York, USA.

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.

PMID:
19465916
PMCID:
PMC2834951
DOI:
10.1038/nsmb.1605
[Indexed for MEDLINE]
Free PMC Article

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