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データを開く
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基本情報
| 登録情報 | データベース: PDB / ID: 7jqc | |||||||||||||||||||||||||||||||||
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| タイトル | SARS-CoV-2 Nsp1, CrPV IRES and rabbit 40S ribosome complex | |||||||||||||||||||||||||||||||||
要素 |
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キーワード | RIBOSOME/VIRAL PROTEIN / cryo-EM / single particle / protein expression inhibition / RIBOSOME-VIRAL PROTEIN complex | |||||||||||||||||||||||||||||||||
| 機能・相同性 | 機能・相同性情報positive regulation of ubiquitin-protein transferase activity / negative regulation of RNA splicing / rRNA modification in the nucleus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / Ribosomal scanning and start codon recognition / laminin receptor activity / Translation initiation complex formation / fibroblast growth factor binding / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation ...positive regulation of ubiquitin-protein transferase activity / negative regulation of RNA splicing / rRNA modification in the nucleus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / Ribosomal scanning and start codon recognition / laminin receptor activity / Translation initiation complex formation / fibroblast growth factor binding / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / Eukaryotic Translation Termination / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / Viral mRNA Translation / 90S preribosome / ubiquitin ligase inhibitor activity / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of signal transduction by p53 class mediator / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / phagocytic cup / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Protein methylation / 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) / translation regulator activity / rough endoplasmic reticulum / ribosomal small subunit export from nucleus / laminin binding / gastrulation / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / IRAK2 mediated activation of TAK1 complex / Prevention of phagosomal-lysosomal fusion / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / MDM2/MDM4 family protein binding / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Endosomal Sorting Complex Required For Transport (ESCRT) / Membrane binding and targetting of GAG proteins / Negative regulation of FLT3 / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / Constitutive Signaling by NOTCH1 HD Domain Mutants / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1,TRAF6-dependent induction of TAK1 complex / cytosolic ribosome / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / Regulation of FZD by ubiquitination / Downregulation of ERBB4 signaling / APC-Cdc20 mediated degradation of Nek2A / p75NTR recruits signalling complexes / InlA-mediated entry of Listeria monocytogenes into host cells / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / TRAF6-mediated induction of TAK1 complex within TLR4 complex / NF-kB is activated and signals survival / Regulation of pyruvate metabolism / Pexophagy / Regulation of innate immune responses to cytosolic DNA / NRIF signals cell death from the nucleus / Downregulation of ERBB2:ERBB3 signaling / Regulation of PTEN localization / VLDLR internalisation and degradation / Activated NOTCH1 Transmits Signal to the Nucleus / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by REV1 / Regulation of BACH1 activity / TICAM1, RIP1-mediated IKK complex recruitment / DNA-(apurinic or apyrimidinic site) lyase / Translesion synthesis by POLK / InlB-mediated entry of Listeria monocytogenes into host cell / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Downregulation of TGF-beta receptor signaling / Josephin domain DUBs / Translesion synthesis by POLI / IKK complex recruitment mediated by RIP1 / Gap-filling DNA repair synthesis and ligation in GG-NER / PINK1-PRKN Mediated Mitophagy / Regulation of activated PAK-2p34 by proteasome mediated degradation / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / positive regulation of apoptotic signaling pathway / TNFR1-induced NF-kappa-B signaling pathway / TCF dependent signaling in response to WNT / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Autodegradation of Cdh1 by Cdh1:APC/C / Regulation of NF-kappa B signaling / APC/C:Cdc20 mediated degradation of Securin 類似検索 - 分子機能 | |||||||||||||||||||||||||||||||||
| 生物種 | ![]() ![]() Cricket paralysis virus (ウイルス) | |||||||||||||||||||||||||||||||||
| 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: 3.3 Å | |||||||||||||||||||||||||||||||||
データ登録者 | Yuan, S. / Xiong, Y. | |||||||||||||||||||||||||||||||||
引用 | ジャーナル: Mol Cell / 年: 2020タイトル: Nonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA. 著者: Shuai Yuan / Lei Peng / Jonathan J Park / Yingxia Hu / Swapnil C Devarkar / Matthew B Dong / Qi Shen / Shenping Wu / Sidi Chen / Ivan B Lomakin / Yong Xiong / ![]() 要旨: The causative virus of the COVID-19 pandemic, SARS-CoV-2, uses its nonstructural protein 1 (Nsp1) to suppress cellular, but not viral, protein synthesis through yet unknown mechanisms. We show here ...The causative virus of the COVID-19 pandemic, SARS-CoV-2, uses its nonstructural protein 1 (Nsp1) to suppress cellular, but not viral, protein synthesis through yet unknown mechanisms. We show here that among all viral proteins, Nsp1 has the largest impact on host viability in the cells of human lung origin. Differential expression analysis of mRNA-seq data revealed that Nsp1 broadly alters the cellular transcriptome. Our cryo-EM structure of the Nsp1-40S ribosome complex shows that Nsp1 inhibits translation by plugging the mRNA entry channel of the 40S. We also determined the structure of the 48S preinitiation complex formed by Nsp1, 40S, and the cricket paralysis virus internal ribosome entry site (IRES) RNA, which shows that it is nonfunctional because of the incorrect position of the mRNA 3' region. Our results elucidate the mechanism of host translation inhibition by SARS-CoV-2 and advance understanding of the impacts from a major pathogenicity factor of SARS-CoV-2. | |||||||||||||||||||||||||||||||||
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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 | 分子: Molmil Jmol/JSmol |
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ダウンロードとリンク
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ダウンロード
| PDBx/mmCIF形式 | 7jqc.cif.gz | 1.8 MB | 表示 | PDBx/mmCIF形式 |
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| PDB形式 | pdb7jqc.ent.gz | 1.4 MB | 表示 | PDB形式 |
| PDBx/mmJSON形式 | 7jqc.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
| その他 | その他のダウンロード |
-検証レポート
| アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/jq/7jqc ftp://data.pdbj.org/pub/pdb/validation_reports/jq/7jqc | HTTPS FTP |
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-関連構造データ
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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 , 2種, 2分子 Ai
| #1: RNA鎖 | 分子量: 602777.875 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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| #28: RNA鎖 | 分子量: 61462.207 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Cricket paralysis virus (ウイルス) / 参照: GenBank: 8895506 |
+タンパク質 , 23種, 23分子 aCDdEfGgHhIJKLNQSTVOPYe
-40S ribosomal protein ... , 5種, 5分子 BbWZM
| #3: タンパク質 | 分子量: 32958.016 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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| #4: タンパク質 | 分子量: 13047.532 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
| #25: タンパク質 | 分子量: 9124.389 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
| #26: タンパク質 | 分子量: 15107.924 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
| #29: タンパク質 | 分子量: 29658.920 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
-Uncharacterized ... , 4種, 4分子 RUXc
| #20: タンパク質 | 分子量: 16477.377 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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| #23: タンパク質 | 分子量: 16106.640 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
| #32: タンパク質 | 分子量: 18133.984 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
| #34: タンパク質 | 分子量: 15844.666 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
-タンパク質・ペプチド , 1種, 1分子 F
| #27: タンパク質・ペプチド | 分子量: 4100.354 Da / 分子数: 1 / Fragment: UNP residues 145-180 / 由来タイプ: 組換発現 由来: (組換発現) ![]() 遺伝子: rep, 1a-1b 発現宿主: ![]() 参照: UniProt: P0DTD1 |
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-詳細
| Has protein modification | 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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| 由来(組換発現) | 生物種: ![]() | ||||||||||||||||||||||||||||||
| 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 | ||||||||||||||||||||||||||||||
| 試料支持 | 詳細: unspecified | ||||||||||||||||||||||||||||||
| 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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
| 電子レンズ | モード: BRIGHT FIELD |
| 撮影 | 電子線照射量: 50 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
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解析
| ソフトウェア | 名称: PHENIX / バージョン: dev_3339: / 分類: 精密化 | ||||||||||||||||||||||||
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| EMソフトウェア | 名称: PHENIX / カテゴリ: モデル精密化 | ||||||||||||||||||||||||
| CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3次元再構成 | 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 48689 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
| 拘束条件 |
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引用
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