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基本情報
登録情報 | ![]() | ||||||||||||||||||||||||||||||||||||||||||
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タイトル | MERS-CoV Nsp1 bound to the human 43S pre-initiation complex | ||||||||||||||||||||||||||||||||||||||||||
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![]() | Nsp1 / MERS / SARS / SARS-CoV2 / ribosome / 40S ribosomal subunit / translation inhibition / coronavirus / 43S PIC / 43S pre-initiation complex / mRNA channel / initiation factor / eIF2 / eIF3 / eIF1 / eIF1A / VIRAL PROTEIN / TRANSLATION | ||||||||||||||||||||||||||||||||||||||||||
機能・相同性 | ![]() male germ cell proliferation / positive regulation of mRNA binding / translation initiation ternary complex / regulation of translation in response to endoplasmic reticulum stress / glial limiting end-foot / HRI-mediated signaling / response to kainic acid / viral translational termination-reinitiation / Cellular response to mitochondrial stress / response to manganese-induced endoplasmic reticulum stress ...male germ cell proliferation / positive regulation of mRNA binding / translation initiation ternary complex / regulation of translation in response to endoplasmic reticulum stress / glial limiting end-foot / HRI-mediated signaling / response to kainic acid / viral translational termination-reinitiation / Cellular response to mitochondrial stress / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / eukaryotic translation initiation factor 3 complex, eIF3e / Response of EIF2AK1 (HRI) to heme deficiency / Recycling of eIF2:GDP / cap-dependent translational initiation / negative regulation of translational initiation in response to stress / PERK-mediated unfolded protein response / methionyl-initiator methionine tRNA binding / eukaryotic translation initiation factor 3 complex, eIF3m / PERK regulates gene expression / IRES-dependent viral translational initiation / translation reinitiation / eukaryotic translation initiation factor 2 complex / eukaryotic translation initiation factor 3 complex / formation of cytoplasmic translation initiation complex / cytoplasmic translational initiation / multi-eIF complex / regulation of translational initiation in response to stress / translation factor activity, RNA binding / eukaryotic 43S preinitiation complex / mRNA cap binding / formation of translation preinitiation complex / eukaryotic 48S preinitiation complex / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of endoplasmic reticulum unfolded protein response / negative regulation of peptidyl-serine phosphorylation / 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 / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / protein tyrosine kinase inhibitor activity / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / nucleolus organization / positive regulation of Golgi to plasma membrane protein transport / translation at postsynapse / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / protein-synthesizing GTPase / metal-dependent deubiquitinase activity / mammalian oogenesis stage / regulation of translational initiation / supercoiled DNA binding / activation-induced cell death of T cells / neural crest cell differentiation / NF-kappaB complex / oxidized purine DNA binding / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / cysteine-type endopeptidase activator activity involved in apoptotic process / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / translation at presynapse / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / negative regulation of phagocytosis / rRNA modification in the nucleus and cytosol / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / pigmentation / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / monocyte chemotaxis / negative regulation of translational frameshifting / Protein hydroxylation / BH3 domain binding / TOR signaling / SARS-CoV-1 modulates host translation machinery / regulation of cell division / mTORC1-mediated signalling / Peptide chain elongation / T cell proliferation involved in immune response / iron-sulfur cluster binding / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / ribosomal small subunit binding 類似検索 - 分子機能 | ||||||||||||||||||||||||||||||||||||||||||
生物種 | ![]() ![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||
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 | ||||||||||||||||||||||||||||||||||||||||||
![]() | 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 | ![]() ![]()
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![]() | ![]() 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: ![]() 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 | ![]() | 337.9 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 85.7 KB 85.7 KB | 表示 表示 | ![]() |
画像 | ![]() | 149.9 KB | ||
マスクデータ | ![]() ![]() | 669.9 MB 669.9 MB | ![]() | |
Filedesc metadata | ![]() | 20.3 KB | ||
その他 | ![]() ![]() | 622.4 MB 622.4 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 1 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1 MB | 表示 | |
XML形式データ | ![]() | 20 KB | 表示 | |
CIF形式データ | ![]() | 23.9 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
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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
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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
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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 |
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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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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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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 |
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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) / 実像数: 8932 / 平均電子線量: 60.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 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 |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: EMDB MAP EMDB ID: |
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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 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |