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- EMDB-11289: SARS-CoV-2 Nsp1 bound to the human CCDC124-80S-eERF1 ribosome complex -
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基本情報
登録情報 | データベース: EMDB / ID: EMD-11289 | ||||||||||||
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タイトル | SARS-CoV-2 Nsp1 bound to the human CCDC124-80S-eERF1 ribosome complex | ||||||||||||
![]() | SARS-CoV-2 Nsp1 bound to the human CCDC124-80S-eERF1 ribosome complex | ||||||||||||
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![]() | Translational Inhibition / SARS-CoV-2 / Immune Evasion / Human Ribosome / VIRAL PROTEIN | ||||||||||||
機能・相同性 | ![]() negative regulation of endoribonuclease activity / CTPase activity / translation termination factor activity / translation release factor complex / cytoplasmic translational termination / regulation of translational termination / OAS antiviral response / translation release factor activity, codon specific / protein methylation / translation release factor activity ...negative regulation of endoribonuclease activity / CTPase activity / translation termination factor activity / translation release factor complex / cytoplasmic translational termination / regulation of translational termination / OAS antiviral response / translation release factor activity, codon specific / protein methylation / translation release factor activity / eukaryotic 80S initiation complex / negative regulation of protein neddylation / 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 / regulation of G1 to G0 transition / axial mesoderm development / negative regulation of formation of translation preinitiation complex / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of respiratory burst involved in inflammatory response / ribosomal protein import into nucleus / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / positive regulation of gastrulation / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / protein-DNA complex disassembly / protein tyrosine kinase inhibitor activity / 90S preribosome assembly / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / nucleolus organization / positive regulation of Golgi to plasma membrane protein transport / sequence-specific mRNA binding / translation at postsynapse / ribosome disassembly / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / mammalian oogenesis stage / GAIT complex / A band / peptidyl-tRNA hydrolase activity / positive regulation of DNA damage response, signal transduction by p53 class mediator / supercoiled DNA binding / activation-induced cell death of T cells / TORC2 complex binding / neural crest cell differentiation / alpha-beta T cell differentiation / NF-kappaB complex / G1 to G0 transition / oxidized purine DNA binding / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / cysteine-type endopeptidase activator activity involved in apoptotic process / middle ear morphogenesis / exit from mitosis / 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 / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / negative regulation of phagocytosis / rRNA modification in the nucleus and cytosol / optic nerve development / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / retinal ganglion cell axon guidance / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / pigmentation / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / homeostatic process / Translation initiation complex formation / response to aldosterone / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / macrophage chemotaxis / positive regulation of activated T cell proliferation / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / lung morphogenesis / male meiosis I / 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 / Peptide chain elongation / T cell proliferation involved in immune response / iron-sulfur cluster binding / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator 類似検索 - 分子機能 | ||||||||||||
生物種 | ![]() ![]() ![]() | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.0 Å | ||||||||||||
![]() | Thoms M / Buschauer R | ||||||||||||
資金援助 | ![]()
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![]() | ![]() 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. | ||||||||||||
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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マップデータ | ![]() | 131 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 118.4 KB 118.4 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 14.2 KB | 表示 | ![]() |
画像 | ![]() | 48.9 KB | ||
Filedesc metadata | ![]() | 21.4 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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「今月の分子」の関連する項目 |
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ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | SARS-CoV-2 Nsp1 bound to the human CCDC124-80S-eERF1 ribosome complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.059 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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試料の構成要素
+全体 : SARS-CoV-2 Nsp1 bound to the human CCDC124-80S-eERF1 ribosome complex
+超分子 #1: SARS-CoV-2 Nsp1 bound to the human CCDC124-80S-eERF1 ribosome complex
+超分子 #2: human CCDC124-80S-eERF1 ribosome complex
+超分子 #3: SARS-CoV-2 Nsp1
+分子 #1: 28S ribosomal RNA
+分子 #2: 5S ribosomal RNA
+分子 #3: 5.8S ribosomal RNA
+分子 #49: 18S ribosomal RNA
+分子 #84: tRNA
+分子 #4: 60S ribosomal protein L8
+分子 #5: 60S ribosomal protein L3
+分子 #6: 60S ribosomal protein L4
+分子 #7: 60S ribosomal protein L5
+分子 #8: 60S ribosomal protein L6
+分子 #9: 60S ribosomal protein L7
+分子 #10: 60S ribosomal protein L7a
+分子 #11: 60S ribosomal protein L9
+分子 #12: 60S ribosomal protein L10-like
+分子 #13: 60S ribosomal protein L11
+分子 #14: 60S ribosomal protein L13
+分子 #15: 60S ribosomal protein L14
+分子 #16: 60S ribosomal protein L15
+分子 #17: 60S ribosomal protein L13a
+分子 #18: 60S ribosomal protein L17
+分子 #19: 60S ribosomal protein L18
+分子 #20: 60S ribosomal protein L19
+分子 #21: 60S ribosomal protein L18a
+分子 #22: 60S ribosomal protein L21
+分子 #23: 60S ribosomal protein L22
+分子 #24: 60S ribosomal protein L23
+分子 #25: 60S ribosomal protein L24
+分子 #26: 60S ribosomal protein L23a
+分子 #27: 60S ribosomal protein L26
+分子 #28: 60S ribosomal protein L27
+分子 #29: 60S ribosomal protein L27a
+分子 #30: 60S ribosomal protein L29
+分子 #31: 60S ribosomal protein L30
+分子 #32: 60S ribosomal protein L31
+分子 #33: 60S ribosomal protein L32
+分子 #34: 60S ribosomal protein L35a
+分子 #35: 60S ribosomal protein L34
+分子 #36: 60S ribosomal protein L35
+分子 #37: 60S ribosomal protein L36
+分子 #38: 60S ribosomal protein L37
+分子 #39: 60S ribosomal protein L38
+分子 #40: 60S ribosomal protein L39
+分子 #41: Ubiquitin-60S ribosomal protein L40
+分子 #42: 60S ribosomal protein L41
+分子 #43: 60S ribosomal protein L36a
+分子 #44: 60S ribosomal protein L37a
+分子 #45: 60S ribosomal protein L28
+分子 #46: 60S acidic ribosomal protein P0
+分子 #47: 60S ribosomal protein L12
+分子 #48: 60S ribosomal protein L10a
+分子 #50: 40S ribosomal protein SA
+分子 #51: 40S ribosomal protein S3a
+分子 #52: 40S ribosomal protein S3
+分子 #53: 40S ribosomal protein S4, X isoform
+分子 #54: 40S ribosomal protein S5
+分子 #55: 40S ribosomal protein S7
+分子 #56: 40S ribosomal protein S8
+分子 #57: 40S ribosomal protein S10
+分子 #58: 40S ribosomal protein S11
+分子 #59: 40S ribosomal protein S15
+分子 #60: 40S ribosomal protein S16
+分子 #61: 40S ribosomal protein S17
+分子 #62: 40S ribosomal protein S18
+分子 #63: 40S ribosomal protein S19
+分子 #64: 40S ribosomal protein S20
+分子 #65: 40S ribosomal protein S21
+分子 #66: 40S ribosomal protein S23
+分子 #67: 40S ribosomal protein S26
+分子 #68: 40S ribosomal protein S28
+分子 #69: 40S ribosomal protein S29
+分子 #70: Receptor of activated protein C kinase 1
+分子 #71: 40S ribosomal protein S2
+分子 #72: 40S ribosomal protein S6
+分子 #73: 40S ribosomal protein S9
+分子 #74: 40S ribosomal protein S12
+分子 #75: 40S ribosomal protein S13
+分子 #76: 40S ribosomal protein S14
+分子 #77: 40S ribosomal protein S15a
+分子 #78: 40S ribosomal protein S24
+分子 #79: 40S ribosomal protein S25
+分子 #80: 40S ribosomal protein S27
+分子 #81: 40S ribosomal protein S30
+分子 #82: Ubiquitin-40S ribosomal protein S27a
+分子 #83: Proliferation-associated protein 2G4
+分子 #85: Coiled-coil domain-containing protein 124
+分子 #86: Non-structural protein 1
+分子 #87: ATP-binding cassette sub-family E member 1
+分子 #88: Eukaryotic peptide chain release factor subunit 1
+分子 #89: MAGNESIUM ION
+分子 #90: ZINC ION
+分子 #91: IRON/SULFUR CLUSTER
+分子 #92: ADENOSINE-5'-DIPHOSPHATE
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 44.8 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |