6ZMI

SARS-CoV-2 Nsp1 bound to the human LYAR-80S ribosome complex

これはPDB形式変換不可エントリーです。

6ZMI の概要

• エントリーDOI: 10.2210/pdb6zmi/pdb
• EMDBエントリー: 11276 11292
• 分子名称: 28S ribosomal RNA, 60S ribosomal protein L7a, 60S ribosomal protein L9, ... (88 entities in total)
• 機能のキーワード: translational inhibition, sars-cov-2, immune evasion, human ribosome, viral protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 86
• 化学式量合計: 3994072.91

構造登録者

Thoms, M.,Buschauer, R.,Ameismeier, M.,Denk, T.,Kratzat, H.,Mackens-Kiani, T.,Cheng, J.,Berninghausen, O.,Becker, T.,Beckmann, R. (登録日: 2020-07-02, 公開日: 2020-08-19, 最終更新日: 2024-05-01)

主引用文献

Thoms, M.,Buschauer, R.,Ameismeier, M.,Koepke, L.,Denk, T.,Hirschenberger, M.,Kratzat, H.,Hayn, M.,Mackens-Kiani, T.,Cheng, J.,Straub, J.H.,Sturzel, C.M.,Frohlich, T.,Berninghausen, O.,Becker, T.,Kirchhoff, F.,Sparrer, K.M.J.,Beckmann, R.
Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2.
Science, 369:1249-1255, 2020

PubMed Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. A major virulence factor of SARS-CoVs is the nonstructural protein 1 (Nsp1), which suppresses host gene expression by ribosome association. Here, we show that Nsp1 from SARS-CoV-2 binds to the 40 ribosomal subunit, resulting in shutdown of messenger RNA (mRNA) translation both in vitro and in cells. Structural analysis by cryo-electron microscopy of in vitro-reconstituted Nsp1-40 and various native Nsp1-40 and -80 complexes revealed that the Nsp1 C terminus binds to and obstructs the mRNA entry tunnel. Thereby, Nsp1 effectively blocks retinoic acid-inducible gene I-dependent innate immune responses that would otherwise facilitate clearance of the infection. Thus, the structural characterization of the inhibitory mechanism of Nsp1 may aid structure-based drug design against SARS-CoV-2.

PubMed: 32680882
DOI: 10.1126/science.abc8665

実験手法

ELECTRON MICROSCOPY (2.6 Å)