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Title | Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2. |
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Journal, issue, pages | Science, Vol. 369, Issue 6508, Page 1249-1255, Year 2020 |
Publish date | Sep 4, 2020 |
Authors | Matthias Thoms / Robert Buschauer / Michael Ameismeier / Lennart Koepke / Timo Denk / Maximilian Hirschenberger / Hanna Kratzat / Manuel Hayn / Timur Mackens-Kiani / Jingdong Cheng / Jan H Straub / Christina M Stürzel / Thomas Fröhlich / Otto Berninghausen / Thomas Becker / Frank Kirchhoff / Konstantin M J Sparrer / Roland Beckmann / |
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 ...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. |
External links | Science / PubMed:32680882 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.6 - 3.2 Å |
Structure data | EMDB-11276, PDB-6zlw: EMDB-11288, PDB-6zm7: EMDB-11289, PDB-6zme: EMDB-11292, PDB-6zmi: EMDB-11299, PDB-6zmo: EMDB-11301, PDB-6zmt: EMDB-11310, PDB-6zn5: EMDB-11325, PDB-6zon: EMDB-11335, PDB-6zp4: |
Chemicals | ChemComp-ZN: ChemComp-MG: ChemComp-SF4: ChemComp-ADP: ChemComp-GTP: |
Source |
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Keywords | VIRAL PROTEIN / Translational Inhibition / SARS-CoV-2 / Immune Evasion / Human Ribosome |