EMD-11299
SARS-CoV-2 Nsp1 bound to the human LYAR-80S-eEF1a ribosome complex
EMD-11299
Single-particle3.1 Å
Deposition: 03/07/2020
Map released: 19/08/2020
Last modified: 01/05/2024
Sample Organism:
Homo sapiens,
Severe acute respiratory syndrome coronavirus 2
Sample: SARS-CoV-2 Nsp1 bound to the human LYAR-80S-eEF1a ribosome complex
Fitted models: 6zmo (Avg. Q-score: 0.519)
Deposition Authors: Thoms M , Buschauer R
Sample: SARS-CoV-2 Nsp1 bound to the human LYAR-80S-eEF1a ribosome complex
Fitted models: 6zmo (Avg. Q-score: 0.519)
Deposition Authors: Thoms M , Buschauer R
Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2.
Thoms M ,
Buschauer R ,
Ameismeier M ,
Koepke L ,
Denk T ,
Hirschenberger M ,
Kratzat H ,
Hayn M,
Mackens-Kiani T ,
Cheng J ,
Straub JH,
Sturzel CM,
Frohlich T ,
Berninghausen O ,
Becker T ,
Kirchhoff F ,
Sparrer KMJ ,
Beckmann R
(2020) Science , 369 , 1249 - 1255
(2020) Science , 369 , 1249 - 1255
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 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.
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.