+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-17805 | ||||||||||||||||||||||||||||||||||||||||||
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タイトル | MERS-CoV Nsp1 bound to the human 43S pre-initiation complex | ||||||||||||||||||||||||||||||||||||||||||
マップデータ | |||||||||||||||||||||||||||||||||||||||||||
試料 |
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キーワード | Nsp1 (ウイルス非構造タンパク質) / MERS / SARS (重症急性呼吸器症候群) / SARS-CoV2 (SARSコロナウイルス2) / ribosome (リボソーム) / 40S ribosomal subunit (リボソーム) / translation inhibition / coronavirus (オルトコロナウイルス亜科) / 43S PIC / 43S pre-initiation complex / mRNA channel / initiation factor / eIF2 / eIF3 (EIF3) / eIF1 / eIF1A / VIRAL PROTEIN (ウイルスタンパク質) / TRANSLATION (翻訳 (生物学)) | ||||||||||||||||||||||||||||||||||||||||||
機能・相同性 | 機能・相同性情報 male germ cell proliferation / positive regulation of mRNA binding / regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / response to kainic acid / viral translational termination-reinitiation / positive regulation of mRNA cis splicing, via spliceosome / response to manganese-induced endoplasmic reticulum stress / eukaryotic translation initiation factor 3 complex, eIF3e ...male germ cell proliferation / positive regulation of mRNA binding / regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / response to kainic acid / viral translational termination-reinitiation / positive regulation of mRNA cis splicing, via spliceosome / response to manganese-induced endoplasmic reticulum stress / eukaryotic translation initiation factor 3 complex, eIF3e / positive regulation of type B pancreatic cell apoptotic process / methionyl-initiator methionine tRNA binding / cap-dependent translational initiation / eukaryotic translation initiation factor 3 complex, eIF3m / Response of EIF2AK1 (HRI) to heme deficiency / translation reinitiation / negative regulation of translational initiation in response to stress / Recycling of eIF2:GDP / PERK-mediated unfolded protein response / : / eukaryotic translation initiation factor 2 complex / IRES-dependent viral translational initiation / PERK regulates gene expression / regulation of translational initiation in response to stress / multi-eIF complex / eukaryotic translation initiation factor 3 complex / eukaryotic 43S preinitiation complex / protein-synthesizing GTPase / cytoplasmic translational initiation / translation factor activity, RNA binding / mRNA cap binding / formation of translation preinitiation complex / formation of cytoplasmic translation initiation 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 / eukaryotic 48S preinitiation complex / 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 / metal-dependent deubiquitinase activity / IRE1-RACK1-PP2A complex / nucleolus organization / : / 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 / 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 / negative regulation of phagocytosis / NF-kappaB complex / rRNA modification in the nucleus and cytosol / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / positive regulation of ubiquitin-protein transferase activity / regulation of translational initiation / 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 / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / 顔料 / protein kinase A binding / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / 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 / fibroblast growth factor binding / positive regulation of activated T cell proliferation / regulation of cell division / protein deubiquitination / ヒドロキシル化 / MTOR / iron-sulfur cluster binding / BH3 domain binding / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Selenocysteine synthesis / monocyte chemotaxis / Formation of a pool of free 40S subunits / cysteine-type endopeptidase activator activity involved in apoptotic process / ribosomal small subunit binding / positive regulation of cyclic-nucleotide phosphodiesterase activity 類似検索 - 分子機能 | ||||||||||||||||||||||||||||||||||||||||||
生物種 | Homo sapiens (ヒト) / Middle East respiratory syndrome-related coronavirus (MERSコロナウイルス) | ||||||||||||||||||||||||||||||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.65 Å | ||||||||||||||||||||||||||||||||||||||||||
データ登録者 | Schubert K / Karousis ED / Ban I / Lapointe CP / Leibundgut M / Baeumlin E / Kummerant E / Scaiola A / Schoenhut T / Ziegelmueller J ...Schubert K / Karousis ED / Ban I / Lapointe CP / Leibundgut M / Baeumlin E / Kummerant E / Scaiola A / Schoenhut T / Ziegelmueller J / Puglisi JD / Muehlemann O / Ban N | ||||||||||||||||||||||||||||||||||||||||||
資金援助 | スイス, 米国, 13件
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引用 | ジャーナル: Mol Cell / 年: 2023 タイトル: Universal features of Nsp1-mediated translational shutdown by coronaviruses. 著者: Katharina Schubert / Evangelos D Karousis / Ivo Ban / Christopher P Lapointe / Marc Leibundgut / Emilie Bäumlin / Eric Kummerant / Alain Scaiola / Tanja Schönhut / Jana Ziegelmüller / ...著者: Katharina Schubert / Evangelos D Karousis / Ivo Ban / Christopher P Lapointe / Marc Leibundgut / Emilie Bäumlin / Eric Kummerant / Alain Scaiola / Tanja Schönhut / Jana Ziegelmüller / Joseph D Puglisi / Oliver Mühlemann / Nenad Ban / 要旨: Nonstructural protein 1 (Nsp1) produced by coronaviruses inhibits host protein synthesis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp1 C-terminal domain was shown to bind the ...Nonstructural protein 1 (Nsp1) produced by coronaviruses inhibits host protein synthesis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp1 C-terminal domain was shown to bind the ribosomal mRNA channel to inhibit translation, but it is unclear whether this mechanism is broadly used by coronaviruses, whether the Nsp1 N-terminal domain binds the ribosome, or how Nsp1 allows viral RNAs to be translated. Here, we investigated Nsp1 from SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and Bat-Hp-CoV coronaviruses using structural, biophysical, and biochemical experiments, revealing a conserved role for the C-terminal domain. Additionally, the N-terminal domain of Bat-Hp-CoV Nsp1 binds to the decoding center of the 40S subunit, where it would prevent mRNA and eIF1A accommodation. Structure-based experiments demonstrated the importance of decoding center interactions in all three coronaviruses and showed that the same regions of Nsp1 are necessary for the selective translation of viral RNAs. Our results provide a mechanistic framework to understand how Nsp1 controls preferential translation of viral RNAs. #1: ジャーナル: Mol.Cell / 年: 2023 タイトル: Universal features of Nsp1-mediated translational shutdown by coronaviruses 著者: Schubert K / Karousis ED / Ban I / Lapointe CP / Leibundgut M / Baeumlin E / Kummerant E / Scaiola A / Schoenhut T / Ziegelmueller J / Puglisi JD / Muehlemann O / Ban N | ||||||||||||||||||||||||||||||||||||||||||
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_17805.map.gz | 337.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-17805-v30.xml emd-17805.xml | 85.7 KB 85.7 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_17805.png | 149.9 KB | ||
マスクデータ | emd_17805_msk_1.map emd_17805_msk_2.map | 669.9 MB 669.9 MB | マスクマップ | |
Filedesc metadata | emd-17805.cif.gz | 20.3 KB | ||
その他 | emd_17805_half_map_1.map.gz emd_17805_half_map_2.map.gz | 622.4 MB 622.4 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-17805 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-17805 | HTTPS FTP |
-関連構造データ
関連構造データ | 8pplMC 8ppkC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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_17805.map.gz / 形式: CCP4 / 大きさ: 669.9 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.065 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
-マスク #1
ファイル | emd_17805_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-マスク #2
ファイル | emd_17805_msk_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_17805_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_17805_half_map_2.map | ||||||||||||
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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 - 43S pre-initiation complex
+超分子 #1: MERS-CoV Nsp1 - 43S pre-initiation complex
+分子 #1: Eukaryotic translation initiation factor 3 subunit K
+分子 #2: Eukaryotic translation initiation factor 3 subunit F
+分子 #3: Eukaryotic translation initiation factor 3 subunit L
+分子 #4: Eukaryotic translation initiation factor 3 subunit M
+分子 #5: Eukaryotic translation initiation factor 3 subunit H
+分子 #6: Eukaryotic translation initiation factor 3 subunit G
+分子 #7: Eukaryotic translation initiation factor 1
+分子 #8: Eukaryotic translation initiation factor 1A, X-chromosomal
+分子 #9: Eukaryotic translation initiation factor 2 subunit 1
+分子 #10: Eukaryotic translation initiation factor 2 subunit 2
+分子 #11: Eukaryotic translation initiation factor 2 subunit 3
+分子 #12: Eukaryotic translation initiation factor 3 subunit A
+分子 #13: Eukaryotic translation initiation factor 3 subunit E
+分子 #15: Eukaryotic translation initiation factor 3 subunit D
+分子 #16: Eukaryotic translation initiation factor 3 subunit C
+分子 #18: 40S ribosomal protein SA
+分子 #19: 40S ribosomal protein S3a
+分子 #20: 40S ribosomal protein S2
+分子 #21: 40S ribosomal protein S3
+分子 #22: 40S ribosomal protein S4, X isoform
+分子 #23: 40S ribosomal protein S5
+分子 #24: 40S ribosomal protein S6
+分子 #25: 40S ribosomal protein S7
+分子 #26: 40S ribosomal protein S8
+分子 #27: 40S ribosomal protein S9
+分子 #28: 40S ribosomal protein S10
+分子 #29: 40S ribosomal protein S11
+分子 #30: 40S ribosomal protein S12
+分子 #31: 40S ribosomal protein S13
+分子 #32: 40S ribosomal protein S14
+分子 #33: 40S ribosomal protein S15
+分子 #34: 40S ribosomal protein S16
+分子 #35: 40S ribosomal protein S17
+分子 #36: Small ribosomal subunit protein uS13
+分子 #37: Small ribosomal subunit protein eS19
+分子 #38: 40S ribosomal protein S20
+分子 #39: 40S ribosomal protein S21
+分子 #40: 40S ribosomal protein S15a
+分子 #41: 40S ribosomal protein S23
+分子 #42: 40S ribosomal protein S24
+分子 #43: 40S ribosomal protein S25
+分子 #44: 40S ribosomal protein S26
+分子 #45: 40S ribosomal protein S27
+分子 #46: 40S ribosomal protein S28
+分子 #47: 40S ribosomal protein S29
+分子 #48: Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein
+分子 #49: Ubiquitin-40S ribosomal protein S27a
+分子 #50: Receptor of activated protein C kinase 1
+分子 #51: 60S ribosomal protein L41
+分子 #52: Host translation inhibitor nsp1
+分子 #14: Met-tRNAi(Met)
+分子 #17: 18S rRNA
+分子 #53: ZINC ION
+分子 #54: GUANOSINE-5'-TRIPHOSPHATE
+分子 #55: MAGNESIUM ION
+分子 #56: METHIONINE
+分子 #57: UNKNOWN ATOM OR ION
+分子 #58: 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: 7.4 構成要素:
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グリッド | モデル: Quantifoil R2/2 / 材質: COPPER / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 15 sec. 詳細: 15 sec in easiGlow Discharge cleaning system (PELCO) at 15 mA | ||||||||
凍結 | 凍結剤: ETHANE-PROPANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV | ||||||||
詳細 | f.c. 100 nM |
-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 / 最大 デフォーカス(公称値): 3.0 µm / 最小 デフォーカス(公称値): 0.6 µm / 倍率(公称値): 81000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 実像数: 8932 / 平均電子線量: 60.0 e/Å2 |
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: EMDB MAP EMDB ID: |
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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
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: 2.65 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 218516 |