E2 Interaction and Dimerization in the Crystal Structure of TRAF6

Journal Article · Thu Jan 01 04:00:00 EST 2009 · Nature Structural and Molecular Biology

DOI:https://doi.org/10.1038/nsmb.1605· OSTI ID:980164

Yin, Q; Lin, S; Lamothe, B; Lu, M; Lo, Y; Hura, G; Zhang, L; Rich, R

Tumor necrosis factor (TNF) receptor-associated factor (TRAF)-6 mediates Lys63-linked polyubiquitination for NF-{kappa}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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 980164
• Report Number(s): BNL--93082-2010-JA
• Journal Information: Nature Structural and Molecular Biology, Journal Name: Nature Structural and Molecular Biology Journal Issue: 6 Vol. 16
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
DIMERIZATION
ENERGY TRANSFER
ENZYMES
FINGERS
FLUORESCENCE
MUTAGENESIS
RESIDUES
RESONANCE
SYMMETRY
SYNTHESIS
ZINC
national synchrotron light source