+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-41039 | |||||||||
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タイトル | MERS-CoV Nsp1 protein bound to the Human 40S Ribosomal subunit | |||||||||
マップデータ | Composite Map | |||||||||
試料 |
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キーワード | MERS-CoV Nsp1 / translation inhibition / 40S ribosome / betacoronaviruses / RIBOSOME / Ribosome-Viral Protein complex | |||||||||
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 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 / endoplasmic reticulum-Golgi intermediate compartment / L13a-mediated translational silencing of Ceruloplasmin expression / GTP hydrolysis and joining of the 60S ribosomal subunit / host cell membrane / 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 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Middle East respiratory syndrome-related coronavirus (ウイルス) | |||||||||
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 | Devarkar SC / Xiong Y | |||||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Cell Rep / 年: 2023 タイトル: Structural basis for translation inhibition by MERS-CoV Nsp1 reveals a conserved mechanism for betacoronaviruses. 著者: Swapnil C Devarkar / Michael Vetick / Shravani Balaji / Ivan B Lomakin / Luojia Yang / Danni Jin / Wendy V Gilbert / Sidi Chen / Yong Xiong / 要旨: All betacoronaviruses (β-CoVs) encode non-structural protein 1 (Nsp1), an essential pathogenicity factor that potently restricts host gene expression. Among the β-CoV family, MERS-CoV is the most ...All betacoronaviruses (β-CoVs) encode non-structural protein 1 (Nsp1), an essential pathogenicity factor that potently restricts host gene expression. Among the β-CoV family, MERS-CoV is the most distantly related member to SARS-CoV-2, and the mechanism for host translation inhibition by MERS-CoV Nsp1 remains controversial. Herein, we show that MERS-CoV Nsp1 directly interacts with the 40S ribosomal subunit. Using cryogenic electron microscopy (cryo-EM), we report a 2.6-Å structure of the MERS-CoV Nsp1 bound to the human 40S ribosomal subunit. The extensive interactions between C-terminal domain of MERS-CoV Nsp1 and the mRNA entry channel of the 40S ribosomal subunit are critical for its translation inhibition function. This mechanism of MERS-CoV Nsp1 is strikingly similar to SARS-CoV and SARS-CoV-2 Nsp1, despite modest sequence conservation. Our results reveal that the mechanism of host translation inhibition is conserved across β-CoVs and highlight a potential therapeutic target for the development of antivirals that broadly restrict β-CoVs. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_41039.map.gz | 100 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-41039-v30.xml emd-41039.xml | 54.2 KB 54.2 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_41039_fsc.xml emd_41039_fsc_2.xml emd_41039_fsc_3.xml | 12.4 KB 12.4 KB 12.4 KB | 表示 表示 表示 | FSCデータファイル |
画像 | emd_41039.png | 67.1 KB | ||
Filedesc metadata | emd-41039.cif.gz | 11.9 KB | ||
その他 | emd_41039_additional_1.map.gz emd_41039_additional_2.map.gz emd_41039_additional_3.map.gz | 106.1 MB 105.9 MB 106 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-41039 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41039 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_41039_validation.pdf.gz | 547.1 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_41039_full_validation.pdf.gz | 546.7 KB | 表示 | |
XML形式データ | emd_41039_validation.xml.gz | 13.6 KB | 表示 | |
CIF形式データ | emd_41039_validation.cif.gz | 18.4 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41039 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41039 | 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_41039.map.gz / 形式: CCP4 / 大きさ: 209.3 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: 1.07 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-追加マップ: 40S Head subvolume
ファイル | emd_41039_additional_1.map | ||||||||||||
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注釈 | 40S Head subvolume | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Consensus Refinement Map
ファイル | emd_41039_additional_2.map | ||||||||||||
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注釈 | Consensus Refinement Map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: 40S Body subvolume
ファイル | emd_41039_additional_3.map | ||||||||||||
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注釈 | 40S Body subvolume | ||||||||||||
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 : MERS-CoV Nsp1 bound to human 40S ribosomal subunit
+超分子 #1: MERS-CoV Nsp1 bound to human 40S ribosomal subunit
+分子 #1: 18S rRNA
+分子 #2: 40S ribosomal protein SA
+分子 #3: 40S ribosomal protein S3a
+分子 #4: 40S ribosomal protein S2
+分子 #5: 40S ribosomal protein S3
+分子 #6: 40S ribosomal protein S4, X isoform
+分子 #7: 40S ribosomal protein S5
+分子 #8: 40S ribosomal protein S6
+分子 #9: 40S ribosomal protein S7
+分子 #10: 40S ribosomal protein S8
+分子 #11: 40S ribosomal protein S9
+分子 #12: 40S ribosomal protein S10
+分子 #13: 40S ribosomal protein S11
+分子 #14: 40S ribosomal protein S12
+分子 #15: 40S ribosomal protein S13
+分子 #16: 40S ribosomal protein S14
+分子 #17: 40S ribosomal protein S15
+分子 #18: 40S ribosomal protein S16
+分子 #19: 40S ribosomal protein S17
+分子 #20: 40S ribosomal protein S18
+分子 #21: 40S ribosomal protein S19
+分子 #22: 40S ribosomal protein S20
+分子 #23: 40S ribosomal protein S21
+分子 #24: 40S ribosomal protein S15a
+分子 #25: 40S ribosomal protein S23
+分子 #26: 40S ribosomal protein S24
+分子 #27: 40S ribosomal protein S25
+分子 #28: 40S ribosomal protein S26
+分子 #29: 40S ribosomal protein S27
+分子 #30: 40S ribosomal protein S28
+分子 #31: 40S ribosomal protein S29
+分子 #32: FAU ubiquitin-like and ribosomal protein S30
+分子 #33: Ubiquitin-40S ribosomal protein S27a
+分子 #34: Receptor of activated protein C kinase 1
+分子 #35: 60S ribosomal protein L41
+分子 #36: Replicase polyprotein 1ab
+分子 #37: MAGNESIUM ION
+分子 #38: ZINC ION
+分子 #39: water
-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 | TFS 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 | C2レンズ絞り径: 70.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 1.8 µm / 最小 デフォーカス(公称値): 0.8 µm / 倍率(公称値): 81000 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |