3hcu
From Proteopedia
Crystal structure of TRAF6 in complex with Ubc13 in the C2 space group
Structural highlights
Function[TRAF6_HUMAN] E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [UBE2N_HUMAN] The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes (By similarity).[11] [12] [13] [14] [15] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedTumor 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. E2 interaction and dimerization in the crystal structure of TRAF6.,Yin Q, Lin SC, Lamothe B, Lu M, Lo YC, Hura G, Zheng L, Rich RL, Campos AD, Myszka DG, Lenardo MJ, Darnay BG, Wu H Nat Struct Mol Biol. 2009 Jun;16(6):658-66. Epub 2009 May 24. PMID:19465916[16] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Large Structures | Ubiquitin--protein ligase | Campos, A D | Darnay, B G | Hura, G | Lamothe, B | Lenardo, M J | Lin, S C | Lo, Y C | Lu, M | Myszka, D G | Rich, R L | Wu, H | Yin, Q | Zheng, L | Atp-binding | Beta-beta-alpha | Coiled coil | Cross-brace | Cytoplasm | Dna damage | Dna repair | Isopeptide bond | Ligase | Metal-binding | Nucleotide-binding | Signaling protein-ligase complex | Ubl conjugation | Ubl conjugation pathway | Zinc | Zinc-finger
