3w31
From Proteopedia
Structual basis for the recognition of Ubc13 by the Shigella flexneri effector OspI
Structural highlights
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).[1] [2] [3] [4] [5] Publication Abstract from PubMedUbc13 is a ubiquitin-conjugating enzyme that plays a key role in the nuclear factor-kappaB signal transduction pathway in human diseases. The Shigella flexneri effector OspI affects inflammatory responses by catalyzing the deamidation of a specific glutamine residue at position 100 in Ubc13 during infection. This modification prevents the activation of the TNF (tumor necrosis factor) receptor-associated factor 6, leading to modulation of the diacylglycerol-CBM (CARD-Bcl10-Malt1) complex-TNF receptor-associated factor 6-nuclear factor-kappaB signaling pathway. To elucidate the structural basis of OspI function, we determined the crystal structures of the catalytically inert OspI C62A mutant and its complex with Ubc13 at resolutions of 3.0 and 2.96A, respectively. The structure of the OspI-Ubc13 complex revealed that the interacting surfaces between OspI and Ubc13 are a hydrophobic surface and a complementary charged surface. Furthermore, we predict that the complementary charged surface of OspI plays a key role in substrate specificity determination. Structural Basis for the Recognition of Ubc13 by the Shigella flexneri Effector OspI.,Nishide A, Kim M, Takagi K, Himeno A, Sanada T, Sasakawa C, Mizushima T J Mol Biol. 2013 Aug 9;425(15):2623-31. doi: 10.1016/j.jmb.2013.02.037. Epub 2013, Mar 27. PMID:23542009[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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