Selected article for: "gene expression and host gene"
Author: Thoms, Matthias; Buschauer, Robert; Ameismeier, Michael; Koepke, Lennart; Denk, Timo; Hirschenberger, Maximilian; Kratzat, Hanna; Hayn, Manuel; Mackens-Kiani, Timur; Cheng, Jingdong; Stürzel, Christina M.; Fröhlich, Thomas; Berninghausen, Otto; Becker, Thomas; Kirchhoff, Frank; Sparrer, Konstantin M.J.; Beckmann, Roland
Title: Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2
  • Cord-id: 1fbf5jcz
  • Document date: 2020_5_18
    • ID: 1fbf5jcz
    Snippet: SARS-CoV-2 is the causative agent of the current COVID-19 pandemic. A major virulence factor of SARS-CoVs is the nonstructural protein 1 (Nsp1) which suppresses host gene expression by ribosome association via an unknown mechanism. Here, we show that Nsp1 from SARS-CoV-2 binds to 40S and 80S ribosomes, resulting in shutdown of capped mRNA translation both in vitro and in cells. Structural analysis by cryo-electron microscopy (cryo-EM) of in vitro reconstituted Nsp1-40S and of native human Nsp1-r
    Document: SARS-CoV-2 is the causative agent of the current COVID-19 pandemic. A major virulence factor of SARS-CoVs is the nonstructural protein 1 (Nsp1) which suppresses host gene expression by ribosome association via an unknown mechanism. Here, we show that Nsp1 from SARS-CoV-2 binds to 40S and 80S ribosomes, resulting in shutdown of capped mRNA translation both in vitro and in cells. Structural analysis by cryo-electron microscopy (cryo-EM) of in vitro reconstituted Nsp1-40S and of native human Nsp1-ribosome complexes revealed that the Nsp1 C-terminus binds to and obstructs the mRNA entry tunnel. Thereby, Nsp1 effectively blocks RIG-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.

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