Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2

doi:10.1126/science.abc8665

GSTDTAP > 气候变化

DOI	10.1126/science.abc8665
	Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2
	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
	2020-09-04
发表期刊	Science
出版年	2020
英文摘要	As the coronavirus disease 2019 (COVID-19) pandemic continues to cause devastation, scientists race to increase their understanding of the disease-causing severe acute respiratory syndrome coronavirus 2. Once inside host cells, not only does the virus hijack the cells' translational machinery to make viral proteins, but the virulence factor nonstructural protein 1 (Nsp1) also shuts down translation of host messenger RNA. Thoms et al. determined a 2.6-angstrom resolution cryo–electron microscopy structure of a reconstituted complex of Nsp1 bound to the human 40 S ribosomal subunit and showed that Nsp1 blocks the messenger RNA entry tunnel. A structural inventory of native Nsp1-ribosome complexes from human cells confirms this mechanism. Cellular studies show that the translational shutdown almost completely inhibits the innate immune response. The binding pocket on the ribosome may be a target for drugs to treat COVID-19. Science , this issue p. [1249][1] 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 S 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 S and various native Nsp1-40 S and -80 S 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. [1]: /lookup/doi/10.1126/science.abc8665
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/293276
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Matthias Thoms,Robert Buschauer,Michael Ameismeier,et al. Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2[J]. Science,2020.
APA	Matthias Thoms.,Robert Buschauer.,Michael Ameismeier.,Lennart Koepke.,Timo Denk.,...&Roland Beckmann.(2020).Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2.Science.
MLA	Matthias Thoms,et al."Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2".Science (2020).