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

Autor: Robert Buschauer, Roland Beckmann, Maximilian Hirschenberger, Thomas Fröhlich, Thomas Becker, Matthias Thoms, Timur Mackens-Kiani, Lennart Koepke, Konstantin M. J. Sparrer, Jan Hendrik Straub, Hanna Kratzat, Manuel Hayn, Michael Ameismeier, Timo Denk, Jingdong Cheng, Otto Berninghausen, Christina M. Stürzel, Frank Kirchhoff
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Models
Molecular
0301 basic medicine
viruses
Pathogenesis
Viral Nonstructural Proteins
Ribosome
Protein Structure
Secondary
0302 clinical medicine
Protein biosynthesis
Receptors
Immunologic
NSP1
Multidisciplinary
Immune evasion
Alphacoronavirus
virus diseases
Microbio
Translation (biology)
Immunevasion
Research Highlight
Cell biology
030220 oncology & carcinogenesis
DEAD Box Protein 58
Interferon
Coronavirus Infections
Structural biology
Protein Binding
Pneumonia
Viral
Biology
Host gene expression
Betacoronavirus
03 medical and health sciences
Protein Domains
Report
Humans
Protein Interaction Domains and Motifs
Eukaryotic Small Ribosomal Subunit
ddc:610
RNA
Messenger
Pandemics
Ribosome Subunits
Small
Eukaryotic
Messenger RNA
Binding Sites
Innate immune system
SARS-CoV-2
Cryoelectron Microscopy
Biochem
COVID-19
RNA
Interferon-beta
Immunity
Innate
Coronavirus
030104 developmental biology
Protein Biosynthesis
DDC 610 / Medicine & health
Pathogenicity
Reports
Zdroj: Science
Signal Transduction and Targeted Therapy
Science (New York, N.y.)
ISSN: 1095-9203
0036-8075
DOI: 10.1126/science.abc8665
Popis: 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 40S 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 Nsp1-40S and various native Nsp1-40S and -80S 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.
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Databáze: OpenAIRE
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