登録情報 データベース : PDB / ID : 6wcz 構造の表示 ダウンロードとリンクタイトル CryoEM structure of full-length ZIKV NS5-hSTAT2 complex 要素Non-structural protein 5 Signal transducer and activator of transcription 2 詳細キーワード IMMUNE SYSTEM / ZIKV NS5 / hSTAT2 / CryoEM機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
ISGF3 complex / symbiont-mediated suppression of host interferon-mediated signaling pathway / Interleukin-20 family signaling / negative regulation of type I interferon-mediated signaling pathway / type I interferon-mediated signaling pathway / regulation of mitochondrial fission / ubiquitin-like protein ligase binding / Regulation of IFNA/IFNB signaling / regulation of protein phosphorylation / flavivirin ... ISGF3 complex / symbiont-mediated suppression of host interferon-mediated signaling pathway / Interleukin-20 family signaling / negative regulation of type I interferon-mediated signaling pathway / type I interferon-mediated signaling pathway / regulation of mitochondrial fission / ubiquitin-like protein ligase binding / Regulation of IFNA/IFNB signaling / regulation of protein phosphorylation / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / cell surface receptor signaling pathway via JAK-STAT / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / ribonucleoside triphosphate phosphatase activity / defense response / Evasion by RSV of host interferon responses / response to peptide hormone / RNA polymerase II transcription regulator complex / Interferon alpha/beta signaling / viral capsid / double-stranded RNA binding / regulation of cell population proliferation / nucleoside-triphosphate phosphatase / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / symbiont-mediated suppression of host toll-like receptor signaling pathway / protein-macromolecule adaptor activity / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / defense response to virus / clathrin-dependent endocytosis of virus by host cell / Potential therapeutics for SARS / methyltransferase cap1 activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / host cell cytoplasm / DNA-binding transcription factor activity, RNA polymerase II-specific / RNA helicase activity / protein dimerization activity / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / RNA helicase / symbiont-mediated suppression of host innate immune response / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA polymerase II cis-regulatory region sequence-specific DNA binding / symbiont entry into host cell / DNA-binding transcription factor activity / symbiont-mediated activation of host autophagy / RNA-directed RNA polymerase / serine-type endopeptidase activity / viral RNA genome replication / RNA-directed RNA polymerase activity / fusion of virus membrane with host endosome membrane / lipid binding / viral envelope / regulation of transcription by RNA polymerase II / chromatin / GTP binding / virion attachment to host cell / host cell nucleus / SARS-CoV-2 activates/modulates innate and adaptive immune responses / virion membrane / structural molecule activity / positive regulation of transcription by RNA polymerase II / ATP hydrolysis activity / proteolysis / extracellular region / nucleoplasm / ATP binding / metal ion binding / identical protein binding / nucleus / membrane / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 Signal transducer and activation of transcription 2, C-terminal / STAT2, SH2 domain / Signal transducer and activator of transcription 2 C terminal / Flavivirus RNA-directed RNA polymerase, thumb domain / STAT transcription factor, DNA-binding, N-terminal / STAT transcription factor, protein interaction / STAT transcription factor, all-alpha domain / STAT transcription factor, DNA-binding / : / STAT transcription factor, coiled-coil domain ... Signal transducer and activation of transcription 2, C-terminal / STAT2, SH2 domain / Signal transducer and activator of transcription 2 C terminal / Flavivirus RNA-directed RNA polymerase, thumb domain / STAT transcription factor, DNA-binding, N-terminal / STAT transcription factor, protein interaction / STAT transcription factor, all-alpha domain / STAT transcription factor, DNA-binding / : / STAT transcription factor, coiled-coil domain / STAT protein, DNA binding domain / STAT protein, protein interaction domain / Signal transducer and activator of transcription, linker domain / STAT protein, protein interaction domain / STAT transcription factor, N-terminal domain superfamily / Transcription factor STAT / STAT transcription factor, coiled coil / p53-like transcription factor, DNA-binding / Flavivirus non-structural protein NS2B / Flavivirus capsid protein C superfamily / Genome polyprotein, Flavivirus / : / Flavivirus non-structural protein NS4A / Flavivirus non-structural protein NS2B / Flavivirus non-structural protein NS4B / mRNA cap 0/1 methyltransferase / Flavivirus non-structural protein NS4B / Flavivirus non-structural protein NS4A / Flavivirus NS2B domain profile. / mRNA cap 0 and cap 1 methyltransferase (EC 2.1.1.56 and EC 2.1.1.57) domain profile. / Flavivirus non-structural protein NS2A / Flavivirus non-structural protein NS2A / Flavivirus NS3, petidase S7 / Peptidase S7, Flavivirus NS3 serine protease / Flavivirus NS3 protease (NS3pro) domain profile. / RNA-directed RNA polymerase, thumb domain, Flavivirus / Flavivirus RNA-directed RNA polymerase, thumb domain / RNA-directed RNA polymerase, flavivirus / Flavivirus RNA-directed RNA polymerase, fingers and palm domains / Flavivirus capsid protein C / Flavivirus capsid protein C / Flavivirus non-structural Protein NS1 / Flavivirus non-structural protein NS1 / Envelope glycoprotein M, flavivirus / Envelope glycoprotein M superfamily, flavivirus / Flavivirus envelope glycoprotein M / Flavivirus polyprotein propeptide / Flavivirus polyprotein propeptide superfamily / Flavivirus polyprotein propeptide / Flavivirus envelope glycoprotein E, stem/anchor domain / : / Flavivirus NS3 helicase, C-terminal helical domain / Flavivirus envelope glycoprotein E, Stem/Anchor domain / Flavivirus envelope glycoprotein E, Stem/Anchor domain superfamily / Flavivirus glycoprotein E, immunoglobulin-like domain / Flavivirus glycoprotein, immunoglobulin-like domain / Flavivirus glycoprotein central and dimerisation domain / Flavivirus glycoprotein, central and dimerisation domains / Flaviviral glycoprotein E, central domain, subdomain 1 / Flaviviral glycoprotein E, central domain, subdomain 2 / Ribosomal RNA methyltransferase, FtsJ domain / FtsJ-like methyltransferase / Flavivirus/Alphavirus glycoprotein, immunoglobulin-like domain superfamily / Flavivirus glycoprotein, central and dimerisation domain superfamily / Flaviviral glycoprotein E, dimerisation domain / DEAD box, Flavivirus / Flavivirus DEAD domain / Vaccinia Virus protein VP39 / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / SH2 domain superfamily / helicase superfamily c-terminal domain / Immunoglobulin E-set / Superfamilies 1 and 2 helicase C-terminal domain profile. / Superfamilies 1 and 2 helicase ATP-binding type-1 domain profile. / DEAD-like helicases superfamily / Helicase, C-terminal / Helicase superfamily 1/2, ATP-binding domain / Alpha-Beta Plaits / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / S-adenosyl-L-methionine-dependent methyltransferase superfamily / Peptidase S1, PA clan / DNA/RNA polymerase superfamily / Rossmann fold / P-loop containing nucleoside triphosphate hydrolase / 2-Layer Sandwich / 3-Layer(aba) Sandwich / Alpha Beta 類似検索 - ドメイン・相同性 Genome polyprotein / Signal transducer and activator of transcription 2 / Genome polyprotein 類似検索 - 構成要素生物種 Homo sapiens (ヒト) Zika virus (ジカ熱ウイルス)手法 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 4 Å 詳細データ登録者 Boxiao, W. / Stephanie, T. / Kang, Z. / Maria, T.S. / Jian, F. / Jiuwei, L. / Linfeng, G. / Wendan, R. / Yanxiang, C. / Ethan, C.V. ...Boxiao, W. / Stephanie, T. / Kang, Z. / Maria, T.S. / Jian, F. / Jiuwei, L. / Linfeng, G. / Wendan, R. / Yanxiang, C. / Ethan, C.V. / HeaJin, H. / Matthew, J.E. / Sean, E.O. / Adolfo, G.S. / Hong, Z. / Rong, H. / Jikui, S. 資金援助 米国, 5件 詳細 詳細を隠す組織 認可番号 国 National Institutes of Health/National Library of Medicine (NIH/NLM) 1S10RR23057 米国 National Institutes of Health/National Library of Medicine (NIH/NLM) 1S10OD018111 米国 National Institutes of Health/National Library of Medicine (NIH/NLM) 1R35GM119721 米国 National Science Foundation (NSF, United States) DBI-1338135 米国 National Institutes of Health/National Library of Medicine (NIH/NLM) 1R21AI147057 米国
引用ジャーナル : Nat Struct Mol Biol / 年 : 2020タイトル : Structural basis for STAT2 suppression by flavivirus NS5.著者: Boxiao Wang / Stephanie Thurmond / Kang Zhou / Maria T Sánchez-Aparicio / Jian Fang / Jiuwei Lu / Linfeng Gao / Wendan Ren / Yanxiang Cui / Ethan C Veit / HeaJin Hong / Matthew J Evans / ... 著者 : Boxiao Wang / Stephanie Thurmond / Kang Zhou / Maria T Sánchez-Aparicio / Jian Fang / Jiuwei Lu / Linfeng Gao / Wendan Ren / Yanxiang Cui / Ethan C Veit / HeaJin Hong / Matthew J Evans / Seán E O'Leary / Adolfo García-Sastre / Z Hong Zhou / Rong Hai / Jikui Song / 要旨 : Suppressing cellular signal transducers of transcription 2 (STAT2) is a common strategy that viruses use to establish infections, yet the detailed mechanism remains elusive, owing to a lack of ... Suppressing cellular signal transducers of transcription 2 (STAT2) is a common strategy that viruses use to establish infections, yet the detailed mechanism remains elusive, owing to a lack of structural information about the viral-cellular complex involved. Here, we report the cryo-EM and crystal structures of human STAT2 (hSTAT2) in complex with the non-structural protein 5 (NS5) of Zika virus (ZIKV) and dengue virus (DENV), revealing two-pronged interactions between NS5 and hSTAT2. First, the NS5 methyltransferase and RNA-dependent RNA polymerase (RdRP) domains form a conserved interdomain cleft harboring the coiled-coil domain of hSTAT2, thus preventing association of hSTAT2 with interferon regulatory factor 9. Second, the NS5 RdRP domain also binds the amino-terminal domain of hSTAT2. Disruption of these ZIKV NS5-hSTAT2 interactions compromised NS5-mediated hSTAT2 degradation and interferon suppression, and viral infection under interferon-competent conditions. Taken together, these results clarify the mechanism underlying the functional antagonism of STAT2 by both ZIKV and DENV. 履歴 登録 2020年3月31日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2020年7月8日 Provider : repository / タイプ : Initial release改定 1.1 2020年10月14日 Group : Database references / カテゴリ : citationItem : _citation.country / _citation.journal_abbrev ... _citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year 改定 1.2 2021年8月25日 Group : Database references / カテゴリ : citation / citation_author / database_2Item : _citation.journal_volume / _citation.page_first ... _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.name / _database_2.pdbx_DOI / _database_2.pdbx_database_accession 改定 1.3 2024年5月29日 Group : Data collection / カテゴリ : chem_comp_atom / chem_comp_bond
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