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SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation.
Nature Structural & Molecular Biology ( IF 16.8 ) Pub Date : 2020-09-09 , DOI: 10.1038/s41594-020-0511-8
Katharina Schubert 1 , Evangelos D Karousis 2 , Ahmad Jomaa 1 , Alain Scaiola 1 , Blanca Echeverria 1 , Lukas-Adrian Gurzeler 2 , Marc Leibundgut 1 , Volker Thiel 3, 4 , Oliver Mühlemann 2 , Nenad Ban 1
Affiliation  

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.



中文翻译:

SARS-CoV-2 Nsp1结合核糖体mRNA通道来抑制翻译。

SARS-CoV-2非结构蛋白1(Nsp1),也称为宿主关闭因子,可抑制宿主先天免疫功能。通过结合低温电子显微镜和生物化学,我们显示SARS-CoV-2 Nsp1结合到核糖体复合物中的人类40S亚基,包括43S预起始复合物和非翻译的80S核糖体。该蛋白质将其C末端结构域插入mRNA通道,从而干扰mRNA结合。我们观察到在体外翻译系统和人类细胞中Nsp1存在下的翻译抑制作用。基于40S–Nsp1复合体的高分辨率结构,我们确定了Nsp1残基对于介导翻译抑制至关重要。我们进一步证明,基因组病毒mRNA的全长5'非翻译区可刺激体外翻译,

更新日期:2020-09-10
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