4whv

E3 ubiquitin-protein ligase RNF8 in complex with Ubiquitin-conjugating enzyme E2 N and Polyubiquitin-BE3 ubiquitin-protein ligase RNF8 in complex with Ubiquitin-conjugating enzyme E2 N and Polyubiquitin-B

Structural highlights 4whv is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 8.3Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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). Publication Abstract from PubMed DNA double-strand break (DSB) responses depend on the sequential actions of the E3 ubiquitin ligases RNF8 and RNF168 plus E2 ubiquitin-conjugating enzyme Ubc13 to specifically generate histone K63-linked ubiquitin chains in DSB signaling. Here we defined the activated RNF8/Ubc13~Ub complex by X-ray crystallography and its functional solution conformations by X-ray scattering, as tested by separation-of-function mutations imaged in cells by immunofluorescence. The collective results show that the RING E3 RNF8 targets E2 Ubc13 to DSB sites and plays a critical role in damage signaling by stimulating polyubiquitination through modulating conformations of ubiquitin covalently linked to the Ubc13 active site. Structure-guided separation-of-function mutations show that the RNF8 E2-stimulating activity is essential for DSB signaling in mammalian cells and necessary for downstream recruitment of 53BP1 and BRCA1. Chromatin targeted RNF168 rescues 53BP1 recruitment involved in non-homologous end joining, but not BRCA1 recruitment for homologous recombination. These findings suggest an allosteric approach to targeting the ubiquitin-docking cleft at the E2:E3 interface for possible interventions in cancer and chronic inflammation, and moreover establish an independent RNF8 role in BRCA1 recruitment. RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity that is Essential for DNA Double-Strand Break Signaling and BRCA1 Tumor Suppressor Recruitment.,Hodge CD, Ismail IH, Edwards RA, Hura GL, Xiao AT, Tainer JA, Hendzel MJ, Glover JN J Biol Chem. 2016 Feb 22. pii: jbc.M116.715698. PMID:26903517 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ubiquitin protein ligase 3D structures 3D structures of ubiquitin 3D structures of ubiquitin conjugating enzyme

spinqualitylabelsall models 4whv, resolution 8.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image