- EMDB-11335: SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome compl... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-11335
タイトル
SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome complex - state 2
マップデータ
SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome complex
試料
複合体: SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome complex - state 2
複合体: human 43S preinitiation ribosome complex - state 2
タンパク質・ペプチド: x 51種
RNA: x 2種
複合体: SARS-CoV-2 Nsp1
タンパク質・ペプチド: x 1種
リガンド: x 3種
キーワード
Translational Inhibition / SARS-CoV-2 / Immune Evasion / Human Ribosome / VIRAL PROTEIN
機能・相同性
機能・相同性情報
male germ cell proliferation / positive regulation of mRNA binding / translation initiation ternary complex / regulation of translation in response to endoplasmic reticulum stress / glial limiting end-foot / HRI-mediated signaling / viral translational termination-reinitiation / Cellular response to mitochondrial stress / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process ...male germ cell proliferation / positive regulation of mRNA binding / translation initiation ternary complex / regulation of translation in response to endoplasmic reticulum stress / glial limiting end-foot / HRI-mediated signaling / viral translational termination-reinitiation / Cellular response to mitochondrial stress / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / eukaryotic translation initiation factor 3 complex, eIF3e / Response of EIF2AK1 (HRI) to heme deficiency / Recycling of eIF2:GDP / cap-dependent translational initiation / negative regulation of translational initiation in response to stress / methionyl-initiator methionine tRNA binding / eukaryotic translation initiation factor 3 complex, eIF3m / PERK-mediated unfolded protein response / PERK regulates gene expression / IRES-dependent viral translational initiation / response to kainic acid / translation reinitiation / eukaryotic translation initiation factor 2 complex / eukaryotic translation initiation factor 3 complex / formation of cytoplasmic translation initiation complex / cytoplasmic translational initiation / multi-eIF complex / regulation of translational initiation in response to stress / translation factor activity, RNA binding / eukaryotic 43S preinitiation complex / mRNA cap binding / formation of translation preinitiation complex / eukaryotic 48S preinitiation complex / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of endoplasmic reticulum unfolded protein response / negative regulation of peptidyl-serine phosphorylation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / protein tyrosine kinase inhibitor activity / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / nucleolus organization / positive regulation of Golgi to plasma membrane protein transport / translation at postsynapse / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / mammalian oogenesis stage / metal-dependent deubiquitinase activity / regulation of translational initiation / protein-synthesizing GTPase / supercoiled DNA binding / activation-induced cell death of T cells / NF-kappaB complex / neural crest cell differentiation / oxidized purine DNA binding / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of ubiquitin-protein transferase activity / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / translation at presynapse / Formation of the ternary complex, and subsequently, the 43S complex / negative regulation of phagocytosis / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / negative regulation of ubiquitin protein ligase activity / protein kinase A binding / ion channel inhibitor activity / Ribosomal scanning and start codon recognition / pigmentation / Translation initiation complex formation / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / positive regulation of activated T cell proliferation / monocyte chemotaxis / negative regulation of translational frameshifting / Protein hydroxylation / BH3 domain binding / TOR signaling / SARS-CoV-1 modulates host translation machinery / regulation of cell division / mTORC1-mediated signalling / T cell proliferation involved in immune response / iron-sulfur cluster binding / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Selenocysteine synthesis / Formation of a pool of free 40S subunits / ribosomal small subunit binding / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) 類似検索 - 分子機能
Eukaryotic translation initiation factor 3 subunit D / Eukaryotic translation initiation factor 3 subunit 7 (eIF-3) / Eukaryotic translation initiation factor 3 subunit H / eIF3h, C-terminal / C-terminal region of eIF3h / Eukaryotic translation initiation factor 3 subunit F / Translation initiation factor 3 complex subunit L / RNA polymerase I-associated factor PAF67 / EIF3I / Eukaryotic translation initiation factor 3 subunit M ...Eukaryotic translation initiation factor 3 subunit D / Eukaryotic translation initiation factor 3 subunit 7 (eIF-3) / Eukaryotic translation initiation factor 3 subunit H / eIF3h, C-terminal / C-terminal region of eIF3h / Eukaryotic translation initiation factor 3 subunit F / Translation initiation factor 3 complex subunit L / RNA polymerase I-associated factor PAF67 / EIF3I / Eukaryotic translation initiation factor 3 subunit M / eIF3 subunit M, C-terminal helix domain / eIF3 subunit 6 N terminal domain / eIF3 subunit M, C-terminal helix / Eukaryotic translation initiation factor 3 subunit E, C-terminal / Eukaryotic translation initiation factor 3 subunit E / Eukaryotic translation initiation factor 3 subunit E, N-terminal / eIF3 subunit 6 N terminal domain / Eukaryotic translation initiation factor 3 subunit K / Translation initiation factor 3, subunit 12, N-terminal, eukaryotic / Eukaryotic translation initiation factor 3 subunit I / Eukaryotic translation initiation factor SUI1 / Eukaryotic translation initiation factor 3 subunit B / eIF3B, RNA recognition motif / Translation initiation factor, beta propellor-like domain / Eukaryotic translation initiation factor eIF2A / SUI1 domain superfamily / Translation initiation factor SUI1 / Translation initiation factor SUI1 family profile. / SUI1 domain / Eukaryotic translation initiation factor 3 subunit M eIF3m/COP9 signalosome complex subunit 7 COPS7 / : / eIF3a, PCI domain, TPR-like region / Eukaryotic translation initiation factor 3 subunit A / Eukaryotic translation initiation factor 3 subunit C, N-terminal domain / Eukaryotic translation initiation factor 3 subunit C / Eukaryotic translation initiation factor 3 subunit 8 N-terminus / Translation initiation factor IF2/IF5 domain / Translation initiation factor IF2/IF5, N-terminal / Translation initiation factor IF2/IF5, zinc-binding / Translation initiation factor IF2/IF5 / Domain found in IF2B/IF5 / domain present in translation initiation factor eIF2B and eIF5 / Translation initiation factor 1A (eIF-1A), conserved site / Eukaryotic initiation factor 1A signature. / eukaryotic translation initiation factor 1A / Translation initiation factor 1A (eIF-1A) / Translation initiation factor 2, alpha subunit / Translation initiation factor 2, alpha subunit, middle domain superfamily / Translation initiation factor 2, alpha subunit, C-terminal / IF2a, S1-like domain / Eukaryotic translation initiation factor 2 alpha subunit / Initiation factor eIF2 gamma, C-terminal / Initiation factor eIF2 gamma, domain 2 / Initiation factor eIF2 gamma, GTP-binding domain / Initiation factor eIF2 gamma, C terminal / : / RNA-binding domain, S1, IF1 type / Translation initiation factor 1A / IF-1 / S1 domain IF1 type profile. / CSN8/PSMD8/EIF3K / CSN8/PSMD8/EIF3K family / Rpn11/EIF3F, C-terminal / Maintenance of mitochondrial structure and function / : / motif in proteasome subunits, Int-6, Nip-1 and TRIP-15 / PCI domain / Proteasome component (PCI) domain / PCI domain profile. / 40S ribosomal protein SA / 40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Translation elongation factor EF1A/initiation factor IF2gamma, C-terminal / Ubiquitin-like protein FUBI / JAB1/Mov34/MPN/PAD-1 ubiquitin protease / S1 domain profile. / : / Ribosomal protein S26e signature. / Ribosomal protein L41 / Ribosomal protein L41 / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. / Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / : / Ribosomal protein S12e signature. / Ribosomal protein S12e / Ribosomal protein S19e, conserved site / Ribosomal protein S19e signature. / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein S5, eukaryotic/archaeal / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Ribosomal protein S2, eukaryotic / S27a-like superfamily / Translation elongation factor EFTu-like, domain 2 / 40S Ribosomal protein S10 / : / Ribosomal protein S7e signature. 類似検索 - ドメイン・相同性
Eukaryotic translation initiation factor 3 subunit F / Eukaryotic translation initiation factor 3 subunit D / Eukaryotic translation initiation factor 3 subunit H / Eukaryotic translation initiation factor 2 subunit 1 / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Replicase polyprotein 1ab / Small ribosomal subunit protein uS5 / Eukaryotic translation initiation factor 2 subunit 2 / Small ribosomal subunit protein uS3 ...Eukaryotic translation initiation factor 3 subunit F / Eukaryotic translation initiation factor 3 subunit D / Eukaryotic translation initiation factor 3 subunit H / Eukaryotic translation initiation factor 2 subunit 1 / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Replicase polyprotein 1ab / Small ribosomal subunit protein uS5 / Eukaryotic translation initiation factor 2 subunit 2 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein eS12 / Small ribosomal subunit protein eS19 / Eukaryotic translation initiation factor 2 subunit 3 / Eukaryotic translation initiation factor 1 / Small ribosomal subunit protein eS27 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS7 / Small ribosomal subunit protein eS10 / Eukaryotic translation initiation factor 1A, X-chromosomal / Eukaryotic translation initiation factor 3 subunit B / Eukaryotic translation initiation factor 3 subunit E / Small ribosomal subunit protein uS10 / Small ribosomal subunit protein eS1 / Small ribosomal subunit protein eS7 / Small ribosomal subunit protein eS8 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein uS9 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS12 / Small ribosomal subunit protein uS13 / Small ribosomal subunit protein uS14 / Small ribosomal subunit protein uS15 / Small ribosomal subunit protein uS17 / Small ribosomal subunit protein eS4, X isoform / Small ribosomal subunit protein eS6 / Small ribosomal subunit protein uS19 / Small ribosomal subunit protein eS24 / Small ribosomal subunit protein eS25 / Small ribosomal subunit protein eS26 / Small ribosomal subunit protein eS28 / Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein / Small ribosomal subunit protein eS32 / Ubiquitin-ribosomal protein eS31 fusion protein / Small ribosomal subunit protein eS21 / Small ribosomal subunit protein RACK1 / Eukaryotic translation initiation factor 3 subunit I / Eukaryotic translation initiation factor 3 subunit A / Eukaryotic translation initiation factor 3 subunit M / Eukaryotic translation initiation factor 3 subunit C / Eukaryotic translation initiation factor 3 subunit K / Eukaryotic translation initiation factor 3 subunit L 類似検索 - 構成要素
生物種
Homo sapiens (ヒト) / Severe acute respiratory syndrome coronavirus 2 (ウイルス)
ジャーナル: Science / 年: 2020 タイトル: Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2. 著者: Matthias Thoms / Robert Buschauer / Michael Ameismeier / Lennart Koepke / Timo Denk / Maximilian Hirschenberger / Hanna Kratzat / Manuel Hayn / Timur Mackens-Kiani / Jingdong Cheng / Jan H ...著者: Matthias Thoms / Robert Buschauer / Michael Ameismeier / Lennart Koepke / Timo Denk / Maximilian Hirschenberger / Hanna Kratzat / Manuel Hayn / Timur Mackens-Kiani / Jingdong Cheng / Jan H Straub / Christina M Stürzel / Thomas Fröhlich / Otto Berninghausen / Thomas Becker / Frank Kirchhoff / Konstantin M J Sparrer / Roland Beckmann / 要旨: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. A major virulence factor of SARS-CoVs is the ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. A major virulence factor of SARS-CoVs is the nonstructural protein 1 (Nsp1), which suppresses host gene expression by ribosome association. Here, we show that Nsp1 from SARS-CoV-2 binds to the 40 ribosomal subunit, resulting in shutdown of messenger RNA (mRNA) translation both in vitro and in cells. Structural analysis by cryo-electron microscopy of in vitro-reconstituted Nsp1-40 and various native Nsp1-40 and -80 complexes revealed that the Nsp1 C terminus binds to and obstructs the mRNA entry tunnel. Thereby, Nsp1 effectively blocks retinoic acid-inducible gene I-dependent innate immune responses that would otherwise facilitate clearance of the infection. Thus, the structural characterization of the inhibitory mechanism of Nsp1 may aid structure-based drug design against SARS-CoV-2.