Tumor necrosis factor (TNF) receptor-associated factor (TRAF)-6 mediates Lys63-linked polyubiquitination for NF-B 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. © 2009 Nature America, Inc. All rights reserved.
CITATION STYLE
Yin, Q., Lin, S. C., Lamothe, B., Lu, M., Lo, Y. C., Hura, G., … Wu, H. (2009). E2 interaction and dimerization in the crystal structure of TRAF6. Nature Structural and Molecular Biology, 16(6), 658–666. https://doi.org/10.1038/nsmb.1605
Mendeley helps you to discover research relevant for your work.