- EMDB-14812: Cryo-EM structure of RCMV-E E27 bound to human DDB1 (deltaBPB) an... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-14812
タイトル
Cryo-EM structure of RCMV-E E27 bound to human DDB1 (deltaBPB) and full-length rat STAT2
マップデータ
DDB1 deltaBPB/E27/STAT2 FL main map
試料
複合体: Ternary complex of RCMV-E E27 with human DDB1 (deltaBPB) and rat STAT2
複合体: DNA damage-binding protein 1
タンパク質・ペプチド: DNA damage-binding protein 1
複合体: E27
タンパク質・ペプチド: B27a
複合体: Signal transducer and activator of transcription
タンパク質・ペプチド: Signal transducer and activator of transcription
リガンド: ZINC ION
機能・相同性
機能・相同性情報
Interleukin-20 family signaling / Interferon alpha/beta signaling / Regulation of IFNA/IFNB signaling / ISGF3 complex / positive regulation by virus of viral protein levels in host cell / epigenetic programming in the zygotic pronuclei / spindle assembly involved in female meiosis / Cul4-RING E3 ubiquitin ligase complex / UV-damage excision repair / biological process involved in interaction with symbiont ...Interleukin-20 family signaling / Interferon alpha/beta signaling / Regulation of IFNA/IFNB signaling / ISGF3 complex / positive regulation by virus of viral protein levels in host cell / epigenetic programming in the zygotic pronuclei / spindle assembly involved in female meiosis / Cul4-RING E3 ubiquitin ligase complex / UV-damage excision repair / biological process involved in interaction with symbiont / WD40-repeat domain binding / regulation of mitotic cell cycle phase transition / Cul4A-RING E3 ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / negative regulation of type I interferon-mediated signaling pathway / regulation of mitochondrial fission / type I interferon-mediated signaling pathway / negative regulation of reproductive process / negative regulation of developmental process / ubiquitin-like protein ligase binding / cullin family protein binding / cell surface receptor signaling pathway via JAK-STAT / viral release from host cell / ectopic germ cell programmed cell death / positive regulation of viral genome replication / positive regulation of gluconeogenesis / proteasomal protein catabolic process / nucleotide-excision repair / Recognition of DNA damage by PCNA-containing replication complex / regulation of protein phosphorylation / DNA Damage Recognition in GG-NER / defense response / regulation of circadian rhythm / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / response to peptide hormone / Wntシグナル経路 / Formation of Incision Complex in GG-NER / cytokine-mediated signaling pathway / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / positive regulation of protein catabolic process / rhythmic process / cellular response to UV / protein-macromolecule adaptor activity / site of double-strand break / Neddylation / regulation of cell population proliferation / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / defense response to virus / chromosome, telomeric region / damaged DNA binding / protein ubiquitination / DNA-binding transcription factor activity, RNA polymerase II-specific / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA修復 / apoptotic process / DNA damage response / protein-containing complex binding / 核小体 / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / positive regulation of transcription by RNA polymerase II / protein-containing complex / DNA binding / extracellular space / extracellular exosome / 核質 / identical protein binding / 細胞核 / 細胞膜 / 細胞質基質 / 細胞質 類似検索 - 分子機能
U5-like protein, herpesvirus / Herpesvirus U5-like family / Signal transducer and activation of transcription 2, C-terminal / STAT2, SH2 domain / Signal transducer and activator of transcription 2 C terminal / STAT transcription factor, DNA-binding, N-terminal / STAT transcription factor, protein interaction / STAT transcription factor, all-alpha domain / STAT transcription factor, DNA-binding / STAT protein, all-alpha domain ...U5-like protein, herpesvirus / Herpesvirus U5-like family / Signal transducer and activation of transcription 2, C-terminal / STAT2, SH2 domain / Signal transducer and activator of transcription 2 C terminal / STAT transcription factor, DNA-binding, N-terminal / STAT transcription factor, protein interaction / STAT transcription factor, all-alpha domain / STAT transcription factor, DNA-binding / STAT protein, all-alpha domain / STAT protein, DNA binding domain / STAT protein, protein interaction domain / STAT protein, protein interaction domain / STAT transcription factor, N-terminal domain superfamily / Transcription factor STAT / STAT transcription factor, coiled coil / Cleavage/polyadenylation specificity factor, A subunit, N-terminal / Mono-functional DNA-alkylating methyl methanesulfonate N-term / Cleavage/polyadenylation specificity factor, A subunit, C-terminal / CPSF A subunit region / p53-like transcription factor, DNA-binding / SH2ドメイン / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2ドメイン / SH2 domain superfamily / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily 類似検索 - ドメイン・相同性
B27a / DNA damage-binding protein 1 / Signal transducer and activator of transcription 類似検索 - 構成要素
生物種
Murid betaherpesvirus 8 (ヘルペスウイルス) / Homo sapiens (ヒト) / Rattus norvegicus (ドブネズミ)
ジャーナル: EMBO J / 年: 2023 タイトル: Structural mechanism of CRL4-instructed STAT2 degradation via a novel cytomegaloviral DCAF receptor. 著者: Vu Thuy Khanh Le-Trilling / Sofia Banchenko / Darius Paydar / Pia Madeleine Leipe / Lukas Binting / Simon Lauer / Andrea Graziadei / Robin Klingen / Christine Gotthold / Jörg Bürger / Thilo ...著者: Vu Thuy Khanh Le-Trilling / Sofia Banchenko / Darius Paydar / Pia Madeleine Leipe / Lukas Binting / Simon Lauer / Andrea Graziadei / Robin Klingen / Christine Gotthold / Jörg Bürger / Thilo Bracht / Barbara Sitek / Robert Jan Lebbink / Anna Malyshkina / Thorsten Mielke / Juri Rappsilber / Christian Mt Spahn / Sebastian Voigt / Mirko Trilling / David Schwefel / 要旨: 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 ...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.
超分子 #4: Signal transducer and activator of transcription
超分子
名称: Signal transducer and activator of transcription / タイプ: complex / ID: 4 / キメラ: Yes / 親要素: 1 / 含まれる分子: #3
由来(天然)
生物種: Rattus norvegicus (ドブネズミ)
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分子 #1: DNA damage-binding protein 1
分子
名称: DNA damage-binding protein 1 / タイプ: protein_or_peptide / ID: 1 詳細: Residues 396-705 from the reference database entry UNP Q16531 have been replaced by a GNGNSG-linker,Residues 396-705 from the reference database entry UNP Q16531 have been replaced by a GNGNSG-linker コピー数: 1 / 光学異性体: LEVO