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基本情報
登録情報 | データベース: PDB / ID: 6zme | ||||||||||||
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タイトル | SARS-CoV-2 Nsp1 bound to the human CCDC124-80S-eERF1 ribosome complex | ||||||||||||
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![]() | VIRAL PROTEIN / Translational Inhibition / SARS-CoV-2 / Immune Evasion / Human Ribosome | ||||||||||||
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 / 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 / sequence-specific mRNA binding / nucleolus organization / positive regulation of Golgi to plasma membrane protein transport / translation at postsynapse / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / TNFR1-mediated ceramide production / ribosome disassembly / 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 / negative regulation of phagocytosis / erythrocyte homeostasis / rRNA modification in the nucleus and cytosol / optic nerve development / laminin receptor activity / cytoplasmic side of rough endoplasmic reticulum membrane / 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 | 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: 3 Å | ||||||||||||
![]() | Thoms, M. / Buschauer, R. / Ameismeier, M. / Denk, T. / Kratzat, H. / Mackens-Kiani, T. / Cheng, J. / Berninghausen, O. / Becker, T. / Beckmann, 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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構造の表示
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 5.1 MB | 表示 | ![]() |
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PDB形式 | ![]() | 表示 | ![]() | |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
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-検証レポート
文書・要旨 | ![]() | 1.6 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.8 MB | 表示 | |
XML形式データ | ![]() | 383.7 KB | 表示 | |
CIF形式データ | ![]() | 679.1 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 11289MC ![]() 6zlwC ![]() 6zm7C ![]() 6zmiC ![]() 6zmoC ![]() 6zmtC ![]() 6zn5C ![]() 6zonC ![]() 6zp4C C: 同じ文献を引用 ( M: このデータのモデリングに利用したマップデータ |
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類似構造データ |
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リンク
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集合体
登録構造単位 | ![]()
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要素
-RNA鎖 , 5種, 5分子 L5L7L8S2CC
#1: RNA鎖 | 分子量: 1638922.000 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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#2: RNA鎖 | 分子量: 38998.078 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#3: RNA鎖 | 分子量: 50449.812 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#49: RNA鎖 | 分子量: 602793.875 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#84: RNA鎖 | 分子量: 24004.262 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
+60S ribosomal protein ... , 43種, 43分子 LALBLCLDLELFLGLHLILJLLLMLNLOLPLQLRLSLTLULVLWLXLYLZLaLbLcLdLe...
-タンパク質 , 9種, 9分子 LmLsSgSfCACECFCICH
#41: タンパク質 | 分子量: 14758.394 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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#46: タンパク質 | 分子量: 34309.418 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#70: タンパク質 | 分子量: 35115.652 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#82: タンパク質 | 分子量: 18004.041 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#83: タンパク質 | 分子量: 43851.879 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#85: タンパク質 | 分子量: 25890.377 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#86: タンパク質 | 分子量: 19801.287 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) ![]() ![]() 参照: UniProt: P0DTD1, ubiquitinyl hydrolase 1, 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; システインプロテアーゼ, SARS coronavirus main proteinase, ...参照: UniProt: P0DTD1, ubiquitinyl hydrolase 1, 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; システインプロテアーゼ, SARS coronavirus main proteinase, RNA-directed RNA polymerase, DNA helicase, RNA helicase, 加水分解酵素; エステル加水分解酵素; 5'-リン酸モノエステル産生エキソリボヌクレアーゼ, 加水分解酵素; エステル加水分解酵素, 転移酵素; 一炭素原子の基を移すもの; メチル基を移すもの |
#87: タンパク質 | 分子量: 67405.234 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#88: タンパク質 | 分子量: 49092.742 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
+40S ribosomal protein ... , 31種, 31分子 SASBSDSESFSHSISKSLSPSQSRSSSTSUSVSXSaScSdSCSGSJSMSNSOSWSYSZSbSe
-非ポリマー , 4種, 267分子 






#89: 化合物 | ChemComp-MG / #90: 化合物 | ChemComp-ZN / #91: 化合物 | #92: 化合物 | ChemComp-ADP / | |
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-詳細
研究の焦点であるリガンドがあるか | N |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 |
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由来(天然) |
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緩衝液 | pH: 7.5 | ||||||||||||||||||||||||
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 44.8 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3次元再構成 | 解像度: 3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 13337 / 対称性のタイプ: POINT |