7JQC

SARS-CoV-2 Nsp1, CrPV IRES and rabbit 40S ribosome complex

Summary for 7JQC

• Entry DOI: 10.2210/pdb7jqc/pdb
• EMDB information: 22432 22433
• Descriptor: rRNA, uS7, eS31, ... (35 entities in total)
• Functional Keywords: cryo-em, single particle, protein expression inhibition, ribosome-viral protein complex, ribosome/viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 35
• Total formula weight: 1290140.39

Authors

Yuan, S.,Xiong, Y. (deposition date: 2020-08-10, release date: 2020-12-02, Last modification date: 2024-03-06)

Primary citation

Yuan, S.,Peng, L.,Park, J.J.,Hu, Y.,Devarkar, S.C.,Dong, M.B.,Shen, Q.,Wu, S.,Chen, S.,Lomakin, I.B.,Xiong, Y.
Nonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA.
Mol.Cell, 80:1055-1066.e6, 2020

PubMed Abstract: 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.

PubMed: 33188728
DOI: 10.1016/j.molcel.2020.10.034

Experimental method

ELECTRON MICROSCOPY (3.3 Å)