+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-11276 | ||||||||||||
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タイトル | SARS-CoV-2 Nsp1 bound to the human 40S ribosomal subunit | ||||||||||||
マップデータ | In vitro reconstituted Nsp1-40S complex. Focused refined map of 40S head. | ||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / 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 / IRE1-RACK1-PP2A complex ...positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / 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 / IRE1-RACK1-PP2A complex / nucleolus organization / response to extracellular stimulus / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / laminin receptor activity / oxidized purine DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / neural crest cell differentiation / NF-kappaB complex / rRNA modification in the nucleus and cytosol / negative regulation of phagocytosis / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / 顔料 / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / phagocytic cup / positive regulation of mitochondrial depolarization / negative regulation of Wnt signaling pathway / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / fibroblast growth factor binding / regulation of cell division / SARS-CoV-1 modulates host translation machinery / iron-sulfur cluster binding / ヒドロキシル化 / MTOR / BH3 domain binding / mTORC1-mediated signalling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Peptide chain elongation / Selenocysteine synthesis / monocyte chemotaxis / cysteine-type endopeptidase activator activity involved in apoptotic process / Formation of a pool of free 40S subunits / ribosomal small subunit export from nucleus / positive regulation of cyclic-nucleotide phosphodiesterase activity / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / translation regulator activity / SRP-dependent cotranslational protein targeting to membrane / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Viral mRNA Translation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / negative regulation of respiratory burst involved in inflammatory response / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / gastrulation / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / spindle assembly / regulation of translational fidelity / MDM2/MDM4 family protein binding / laminin binding / Protein methylation / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / 小胞体 / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Nuclear events stimulated by ALK signaling in cancer / negative regulation of smoothened signaling pathway / rescue of stalled ribosome / signaling adaptor activity / positive regulation of cell cycle / negative regulation of peptidyl-serine phosphorylation / stress granule assembly / translation initiation factor binding / maturation of SSU-rRNA / positive regulation of intrinsic apoptotic signaling pathway / Mitotic Prometaphase / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / EML4 and NUDC in mitotic spindle formation / positive regulation of apoptotic signaling pathway / negative regulation of ubiquitin-dependent protein catabolic process / Maturation of protein E / positive regulation of microtubule polymerization 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) / Severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2) / Human (ヒト) | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.6 Å | ||||||||||||
データ登録者 | 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 | ドイツ, 3件
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引用 | 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. | ||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_11276.map.gz | 164.3 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-11276-v30.xml emd-11276.xml | 56.1 KB 56.1 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_11276.png | 49.4 KB | ||
その他 | emd_11276_additional_1.map.gz emd_11276_additional_2.map.gz emd_11276_additional_3.map.gz | 8.1 MB 2.4 MB 96.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-11276 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-11276 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_11276.map.gz / 形式: CCP4 / 大きさ: 244.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | In vitro reconstituted Nsp1-40S complex. Focused refined map of 40S head. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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-添付データ
-追加マップ: In vitro reconstituted Nsp1-40S complex. Focused refined map...
ファイル | emd_11276_additional_1.map | ||||||||||||
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注釈 | In vitro reconstituted Nsp1-40S complex. Focused refined map of 40S body. | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Native Nsp1-40S complex.
ファイル | emd_11276_additional_2.map | ||||||||||||
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注釈 | Native Nsp1-40S complex. | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Native Nsp1-40S complex.
ファイル | emd_11276_additional_3.map | ||||||||||||
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注釈 | Native Nsp1-40S complex. | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
+全体 : SARS-CoV-2 Nsp1 bound to the human 40S ribosomal subunit
+超分子 #1: SARS-CoV-2 Nsp1 bound to the human 40S ribosomal subunit
+超分子 #2: Human 40S ribosomal subunit
+超分子 #3: SARS-CoV-2 Nsp1
+分子 #1: 40S ribosomal protein SA
+分子 #2: 40S ribosomal protein S3a
+分子 #3: 40S ribosomal protein S2
+分子 #4: 40S ribosomal protein S4, X isoform
+分子 #5: 40S ribosomal protein S3
+分子 #6: 40S ribosomal protein S6
+分子 #7: 40S ribosomal protein S7
+分子 #8: 40S ribosomal protein S8
+分子 #9: 40S ribosomal protein S9
+分子 #10: 40S ribosomal protein S5
+分子 #11: 40S ribosomal protein S11
+分子 #12: 40S ribosomal protein S10
+分子 #13: 40S ribosomal protein S13
+分子 #14: 40S ribosomal protein S12
+分子 #15: 40S ribosomal protein S14
+分子 #16: 40S ribosomal protein S15
+分子 #17: 40S ribosomal protein S16
+分子 #18: 40S ribosomal protein S17
+分子 #19: 40S ribosomal protein S18
+分子 #20: 40S ribosomal protein S19
+分子 #21: 40S ribosomal protein S20
+分子 #22: 40S ribosomal protein S15a
+分子 #23: 40S ribosomal protein S23
+分子 #24: 40S ribosomal protein S24
+分子 #25: 40S ribosomal protein S21
+分子 #26: 40S ribosomal protein S25
+分子 #27: 40S ribosomal protein S27
+分子 #28: 40S ribosomal protein S26
+分子 #29: 40S ribosomal protein S28
+分子 #30: 40S ribosomal protein S30
+分子 #31: 40S ribosomal protein S29
+分子 #32: Ubiquitin-40S ribosomal protein S27a
+分子 #33: 60S ribosomal protein L41
+分子 #34: Receptor of activated protein C kinase 1
+分子 #36: Non-structural protein 1
+分子 #35: 18S ribosomal RNA
+分子 #37: ZINC ION
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy |
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 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
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最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 173060 |