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TitleNonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA.
Journal, issue, pagesMol Cell, Vol. 80, Issue 6, Page 1055-11066.e6, Year 2020
Publish dateDec 17, 2020
AuthorsShuai Yuan / Lei Peng / Jonathan J Park / Yingxia Hu / Swapnil C Devarkar / Matthew B Dong / Qi Shen / Shenping Wu / Sidi Chen / Ivan B Lomakin / Yong Xiong /
PubMed AbstractThe causative virus of the COVID-19 pandemic, SARS-CoV-2, uses its nonstructural protein 1 (Nsp1) to suppress cellular, but not viral, protein synthesis through yet unknown mechanisms. We show here ...The causative virus of the COVID-19 pandemic, SARS-CoV-2, uses its nonstructural protein 1 (Nsp1) to suppress cellular, but not viral, protein synthesis through yet unknown mechanisms. We show here that among all viral proteins, Nsp1 has the largest impact on host viability in the cells of human lung origin. Differential expression analysis of mRNA-seq data revealed that Nsp1 broadly alters the cellular transcriptome. Our cryo-EM structure of the Nsp1-40S ribosome complex shows that Nsp1 inhibits translation by plugging the mRNA entry channel of the 40S. We also determined the structure of the 48S preinitiation complex formed by Nsp1, 40S, and the cricket paralysis virus internal ribosome entry site (IRES) RNA, which shows that it is nonfunctional because of the incorrect position of the mRNA 3' region. Our results elucidate the mechanism of host translation inhibition by SARS-CoV-2 and advance understanding of the impacts from a major pathogenicity factor of SARS-CoV-2.
External linksMol Cell / PubMed:33188728 / PubMed Central
MethodsEM (single particle)
Resolution2.7 - 3.3 Å
Structure data

22432

7jqb

EMDB-22432, PDB-7jqb:
SARS-CoV-2 Nsp1 and rabbit 40S ribosome complex
Method: EM (single particle) / Resolution: 2.7 Å

22433

7jqc

EMDB-22433, PDB-7jqc:
SARS-CoV-2 Nsp1, CrPV IRES and rabbit 40S ribosome complex
Method: EM (single particle) / Resolution: 3.3 Å

Source
  • severe acute respiratory syndrome coronavirus 2
  • oryctolagus cuniculus (rabbit)
  • cricket paralysis virus
KeywordsRIBOSOME/VIRAL PROTEIN / cryo-EM / single particle / protein expression inhibition / RIBOSOME-VIRAL PROTEIN complex

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