+検索条件
-Structure paper
タイトル | SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation. |
---|---|
ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 27, Issue 10, Page 959-966, Year 2020 |
掲載日 | 2020年9月9日 |
著者 | Katharina Schubert / Evangelos D Karousis / Ahmad Jomaa / Alain Scaiola / Blanca Echeverria / Lukas-Adrian Gurzeler / Marc Leibundgut / Volker Thiel / Oliver Mühlemann / Nenad Ban / |
PubMed 要旨 | The SARS-CoV-2 non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, suppresses host innate immune functions. By combining cryo-electron microscopy and biochemistry, we show ...The SARS-CoV-2 non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, suppresses host innate immune functions. By combining cryo-electron microscopy and biochemistry, we show that SARS-CoV-2 Nsp1 binds to the human 40S subunit in ribosomal complexes, including the 43S pre-initiation complex and the non-translating 80S ribosome. The protein inserts its C-terminal domain into the mRNA channel, where it interferes with mRNA binding. We observe translation inhibition in the presence of Nsp1 in an in vitro translation system and in human cells. Based on the high-resolution structure of the 40S-Nsp1 complex, we identify residues of Nsp1 crucial for mediating translation inhibition. We further show that the full-length 5' untranslated region of the genomic viral mRNA stimulates translation in vitro, suggesting that SARS-CoV-2 combines global inhibition of translation by Nsp1 with efficient translation of the viral mRNA to allow expression of viral genes. |
リンク | Nat Struct Mol Biol / PubMed:32908316 |
手法 | EM (単粒子) |
解像度 | 2.5 - 4.1 Å |
構造データ | EMDB-11320, PDB-6zoj: EMDB-11321, PDB-6zok: EMDB-11322, PDB-6zol: EMDB-11323: EMDB-11609: |
化合物 | ChemComp-MG: ChemComp-ZN: |
由来 |
|
キーワード | TRANSLATION / inhibitor / mRNA channel / 40S ribosomal subunit |