+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-22681 | |||||||||
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タイトル | SARS-COV-2 nsp1 in complex with human 40S ribosome | |||||||||
マップデータ | composite map | |||||||||
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 respiratory burst involved in inflammatory response / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation ...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 respiratory burst involved in inflammatory response / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / IRE1-RACK1-PP2A complex / : / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / oxidized purine DNA binding / supercoiled DNA binding / neural crest cell differentiation / NF-kappaB complex / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / protein kinase A binding / Translation initiation complex formation / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / ion channel inhibitor activity / pigmentation / mammalian oogenesis stage / positive regulation of mitochondrial depolarization / activation-induced cell death of T cells / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / iron-sulfur cluster binding / regulation of cell division / Protein hydroxylation / negative regulation of peptidyl-serine phosphorylation / BH3 domain binding / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Peptide chain elongation / monocyte chemotaxis / Selenocysteine synthesis / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / Formation of a pool of free 40S subunits / phagocytic cup / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of respiratory burst involved in inflammatory response / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Viral mRNA Translation / L13a-mediated translational silencing of Ceruloplasmin expression / GTP hydrolysis and joining of the 60S ribosomal subunit / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / TOR signaling / T cell proliferation involved in immune response / Major pathway of rRNA processing in the nucleolus and cytosol / spindle assembly / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of translational fidelity / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / ribosomal small subunit export from nucleus / erythrocyte development / translation regulator activity / Protein methylation / Nuclear events stimulated by ALK signaling in cancer / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / cytosolic ribosome / positive regulation of cell cycle / signaling adaptor activity / negative regulation of smoothened signaling pathway / stress granule assembly / positive regulation of intrinsic apoptotic signaling pathway / Mitotic Prometaphase / laminin binding / rough endoplasmic reticulum / 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) / EML4 and NUDC in mitotic spindle formation / Maturation of protein E / positive regulation of JUN kinase activity / Maturation of protein E / gastrulation / ER Quality Control Compartment (ERQC) / MDM2/MDM4 family protein binding 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Severe acute respiratory syndrome coronavirus 2 (ウイルス) / 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: 2.9 Å | |||||||||
データ登録者 | Wang L / Shi M / Wu H | |||||||||
引用 | ジャーナル: bioRxiv / 年: 2020 タイトル: SARS-CoV-2 Nsp1 suppresses host but not viral translation through a bipartite mechanism. 著者: Ming Shi / Longfei Wang / Pietro Fontana / Setu Vora / Ying Zhang / Tian-Min Fu / Judy Lieberman / Hao Wu / 要旨: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly contagious virus that underlies the current COVID-19 pandemic. SARS-CoV-2 is thought to disable various features of host ...The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly contagious virus that underlies the current COVID-19 pandemic. SARS-CoV-2 is thought to disable various features of host immunity and cellular defense. The SARS-CoV-2 nonstructural protein 1 (Nsp1) is known to inhibit host protein translation and could be a target for antiviral therapy against COVID-19. However, how SARS-CoV-2 circumvents this translational blockage for the production of its own proteins is an open question. Here, we report a bipartite mechanism of SARS-CoV-2 Nsp1 which operates by: (1) hijacking the host ribosome via direct interaction of its C-terminal domain (CT) with the 40S ribosomal subunit and (2) specifically lifting this inhibition for SARS-CoV-2 via a direct interaction of its N-terminal domain (NT) with the 5' untranslated region (5' UTR) of SARS-CoV-2 mRNA. We show that while Nsp1-CT is sufficient for binding to 40S and inhibition of host protein translation, the 5' UTR of SARS-CoV-2 mRNA removes this inhibition by binding to Nsp1-NT, suggesting that the Nsp1-NT-UTR interaction is incompatible with the Nsp1-CT-40S interaction. Indeed, lengthening the linker between Nsp1-NT and Nsp1-CT of Nsp1 progressively reduced the ability of SARS-CoV-2 5' UTR to escape the translational inhibition, supporting that the incompatibility is likely steric in nature. The short SL1 region of the 5' UTR is required for viral mRNA translation in the presence of Nsp1. Thus, our data provide a comprehensive view on how Nsp1 switches infected cells from host mRNA translation to SARS-CoV-2 mRNA translation, and that Nsp1 and 5' UTR may be targeted for anti-COVID-19 therapeutics. | |||||||||
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_22681.map.gz | 169.6 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-22681-v30.xml emd-22681.xml | 47.5 KB 47.5 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_22681.png | 177.1 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-22681 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22681 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_22681_validation.pdf.gz | 358.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_22681_full_validation.pdf.gz | 357.8 KB | 表示 | |
XML形式データ | emd_22681_validation.xml.gz | 7 KB | 表示 | |
CIF形式データ | emd_22681_validation.cif.gz | 8 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22681 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22681 | 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_22681.map.gz / 形式: CCP4 / 大きさ: 178 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | composite map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.08 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
-試料の構成要素
+全体 : complex of SARS-CoV-2 Nsp1 and human 40S ribosome
+超分子 #1: complex of SARS-CoV-2 Nsp1 and human 40S ribosome
+超分子 #2: human 40S ribosome
+超分子 #3: SARS-CoV-2 Nsp1
+分子 #1: 40S ribosomal protein S17
+分子 #3: 40S ribosomal protein S29
+分子 #4: 40S ribosomal protein S3
+分子 #5: 40S ribosomal protein S5
+分子 #6: 40S ribosomal protein S10
+分子 #7: 40S ribosomal protein S12
+分子 #8: 40S ribosomal protein S15
+分子 #9: 40S ribosomal protein S16
+分子 #10: 40S ribosomal protein S18
+分子 #11: 40S ribosomal protein S19
+分子 #12: 40S ribosomal protein S20
+分子 #13: 40S ribosomal protein S25
+分子 #14: 40S ribosomal protein S28
+分子 #15: 40S ribosomal protein S27a
+分子 #16: Receptor of activated protein C kinase 1
+分子 #17: 40S ribosomal protein SA
+分子 #18: 40S ribosomal protein S3a
+分子 #19: 40S ribosomal protein S2
+分子 #20: 40S ribosomal protein S4, X isoform
+分子 #21: 40S ribosomal protein S6
+分子 #22: 40S ribosomal protein S7
+分子 #23: 40S ribosomal protein S8
+分子 #24: 40S ribosomal protein S9
+分子 #25: 40S ribosomal protein S11
+分子 #26: 40S ribosomal protein S13
+分子 #27: 40S ribosomal protein S14
+分子 #28: 40S ribosomal protein S21
+分子 #29: 40S ribosomal protein S15a
+分子 #30: 40S ribosomal protein S23
+分子 #31: 40S ribosomal protein S24
+分子 #32: 40S ribosomal protein S26
+分子 #33: 40S ribosomal protein S27
+分子 #34: 40S ribosomal protein S30
+分子 #35: 60S ribosomal protein L41
+分子 #36: Host translation inhibitor nsp1
+分子 #2: 40S ribosomal rRNA18S
+分子 #37: MAGNESIUM ION
+分子 #38: 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: 7.4 |
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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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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 50.0 e/Å2 |
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: SPOT SCAN / 撮影モード: BRIGHT FIELD |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: PDB ENTRY PDBモデル - PDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 794651 |
初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |