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-Structure paper
タイトル | Universal features of Nsp1-mediated translational shutdown by coronaviruses. |
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ジャーナル・号・ページ | Mol Cell, Vol. 83, Issue 19, Page 3546-33557.e8, Year 2023 |
掲載日 | 2023年10月5日 |
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 / |
PubMed 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. |
リンク | Mol Cell / PubMed:37802027 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.65 - 2.98 Å |
構造データ | EMDB-17804, PDB-8ppk: EMDB-17805, PDB-8ppl: |
化合物 | ChemComp-UNX: ChemComp-MG: ChemComp-ZN: ChemComp-GTP: ChemComp-MET: ChemComp-HOH: |
由来 |
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キーワード | TRANSLATION (翻訳 (生物学)) / 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) |