7znn

Cryo-EM structure of RCMV-E E27 bound to human DDB1 (deltaBPB) and full-length rat STAT2

spinqualitylabelsall models 7znn, resolution 4.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7znn is a 3 chain structure with sequence from Homo sapiens, Murid betaherpesvirus 8 and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.8Å Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DDB1_HUMAN Required for DNA repair. Binds to DDB2 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). May also play a role in ubiquitination of CDKN1B/p27kip when associated with CUL4 and SKP2. Publication Abstract from PubMed Human cytomegalovirus (CMV) is a ubiquitously distributed pathogen whose rodent counterparts such as mouse and rat CMV serve as common infection models. Here, we conducted global proteome profiling of rat CMV-infected cells and uncovered a pronounced loss of the transcription factor STAT2, which is crucial for antiviral interferon signalling. Via deletion mutagenesis, we found that the viral protein E27 is required for CMV-induced STAT2 depletion. Cellular and in vitro analyses showed that E27 exploits host-cell Cullin4-RING ubiquitin ligase (CRL4) complexes to induce poly-ubiquitylation and proteasomal degradation of STAT2. Cryo-electron microscopy revealed how E27 mimics molecular surface properties of cellular CRL4 substrate receptors called DCAFs (DDB1- and Cullin4-associated factors), thereby displacing them from the catalytic core of CRL4. Moreover, structural analyses showed that E27 recruits STAT2 through a bipartite binding interface, which partially overlaps with the IRF9 binding site. Structure-based mutations in M27, the murine CMV homologue of E27, impair the interferon-suppressing capacity and virus replication in mouse models, supporting the conserved importance of DCAF mimicry for CMV immune evasion. Structural mechanism of CRL4-instructed STAT2 degradation via a novel cytomegaloviral DCAF receptor.,Le-Trilling VTK, Banchenko S, Paydar D, Leipe PM, Binting L, Lauer S, Graziadei A, Klingen R, Gotthold C, Burger J, Bracht T, Sitek B, Jan Lebbink R, Malyshkina A, Mielke T, Rappsilber J, Spahn CM, Voigt S, Trilling M, Schwefel D EMBO J. 2023 Mar 1;42(5):e112351. doi: 10.15252/embj.2022112351. Epub 2023 Feb , 10. PMID:36762436 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA damage-binding protein

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