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基本情報
登録情報 | データベース: PDB / ID: 7jqb | |||||||||||||||||||||||||||||||||
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タイトル | SARS-CoV-2 Nsp1 and rabbit 40S ribosome complex | |||||||||||||||||||||||||||||||||
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![]() | RIBOSOME/VIRAL PROTEIN / cryo-EM / single particle / protein expression inhibition / RIBOSOME-VIRAL PROTEIN complex | |||||||||||||||||||||||||||||||||
機能・相同性 | ![]() ribosomal subunit / negative regulation of RNA splicing / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / rRNA modification in the nucleus and cytosol / laminin receptor activity / Ribosomal scanning and start codon recognition / Translation initiation complex formation / fibroblast growth factor binding / SARS-CoV-1 modulates host translation machinery ...ribosomal subunit / negative regulation of RNA splicing / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / rRNA modification in the nucleus and cytosol / laminin receptor activity / Ribosomal scanning and start codon recognition / Translation initiation complex formation / fibroblast growth factor binding / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / phagocytic cup / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / 90S preribosome / 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 / 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) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Protein methylation / ribosomal small subunit export from nucleus / rough endoplasmic reticulum / laminin binding / translation regulator activity / gastrulation / Maturation of protein E / Maturation of protein E / MDM2/MDM4 family protein binding / cytosolic ribosome / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Endosomal Sorting Complex Required For Transport (ESCRT) / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Negative regulation of FLT3 / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1,TRAF6-dependent induction of TAK1 complex / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / Regulation of FZD by ubiquitination / Downregulation of ERBB4 signaling / p75NTR recruits signalling complexes / APC-Cdc20 mediated degradation of Nek2A / InlA-mediated entry of Listeria monocytogenes into host cells / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / TRAF6-mediated induction of TAK1 complex within TLR4 complex / Regulation of pyruvate metabolism / Regulation of innate immune responses to cytosolic DNA / NF-kB is activated and signals survival / Downregulation of ERBB2:ERBB3 signaling / Pexophagy / NRIF signals cell death from the nucleus / 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 / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / TICAM1, RIP1-mediated IKK complex recruitment / Translesion synthesis by REV1 / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Translesion synthesis by POLK / InlB-mediated entry of Listeria monocytogenes into host cell / Downregulation of TGF-beta receptor signaling / Josephin domain DUBs / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / positive regulation of apoptotic signaling pathway / Regulation of activated PAK-2p34 by proteasome mediated degradation / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Translesion synthesis by POLI / IKK complex recruitment mediated by RIP1 / Gap-filling DNA repair synthesis and ligation in GG-NER / PINK1-PRKN Mediated Mitophagy / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / TNFR1-induced NF-kappa-B signaling pathway / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / TCF dependent signaling in response to WNT 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: 2.7 Å | |||||||||||||||||||||||||||||||||
![]() | Yuan, S. / Xiong, Y. | |||||||||||||||||||||||||||||||||
![]() | ![]() 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. | |||||||||||||||||||||||||||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | 分子: ![]() ![]() |
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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 | ![]() | 1.7 MB | 表示 | ![]() |
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PDB形式 | ![]() | 1.3 MB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | 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
+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) ![]() ![]() |
#28: 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) ![]() ![]() |
#31: 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) ![]() ![]() |
#33: 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) ![]() ![]() |
-RNA鎖 / タンパク質・ペプチド , 2種, 2分子 AF
#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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#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 |
-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: ![]() |
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: 2.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 353927 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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