7x6y

TRIM7 in complex with C-terminal peptide of NSP5

spinqualitylabelsall models 7x6y, resolution 1.39Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7x6y is a 2 chain structure with sequence from Homo sapiens and Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.39Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TRIM7_HUMAN E3 ubiquitin-protein ligase. Mediates 'Lys-63'-linked polyubiquitination and stabilization of the JUN coactivator RNF187 in response to growth factor signaling via the MEK/ERK pathway, thereby regulating JUN transactivation and cellular proliferation (PubMed:25851810). Promotes the TLR4-mediated signaling activation through its E3 ligase domain leading to production of proinflammatory cytokines and type I interferon (By similarity). Plays also a negative role in the regulation of exogenous cytosolic DNA virus-triggered immune response. Mechanistically, enhances the 'Lys-48'-linked ubiquitination of STING1 leading to its proteasome-dependent degradation (PubMed:32126128).[UniProtKB:Q923T7] (Microbial infection) Promotes Zika virus replication by mediating envelope protein E ubiquitination. Publication Abstract from PubMed The E3 ligase TRIM7 has emerged as a critical player in viral infection and pathogenesis. However, the mechanism governing the TRIM7-substrate association remains to be defined. Here we report the crystal structures of TRIM7 in complex with 2C peptides of human enterovirus. Structure-guided studies reveal the C-terminal glutamine residue of 2C as the primary determinant for TRIM7 binding. Leveraged by this finding, we identify norovirus and SARS-CoV-2 proteins, and physiological proteins, as new TRIM7 substrates. Crystal structures of TRIM7 in complex with multiple peptides derived from SARS-CoV-2 proteins display the same glutamine-end recognition mode. Furthermore, TRIM7 could trigger the ubiquitination and degradation of these substrates, possibly representing a new Gln/C-degron pathway. Together, these findings unveil a common recognition mode by TRIM7, providing the foundation for further mechanistic characterization of antiviral and cellular functions of TRIM7. A C-terminal glutamine recognition mechanism revealed by E3 ligase TRIM7 structures.,Liang X, Xiao J, Li X, Liu Y, Lu Y, Wen Y, Li Z, Che X, Ma Y, Zhang X, Zhang Y, Jian D, Wang P, Xuan C, Yu G, Li L, Zhang H Nat Chem Biol. 2022 Aug 18. pii: 10.1038/s41589-022-01128-x. doi:, 10.1038/s41589-022-01128-x. PMID:35982226 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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