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- PDB-6zp4: SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome compl... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6zp4 | ||||||||||||
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Title | SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome complex - state 2 | ||||||||||||
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Function / homology | ![]() male germ cell proliferation / translation initiation ternary complex / cap-dependent translational initiation / glial limiting end-foot / viral translational termination-reinitiation / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / negative regulation of translational initiation in response to stress / eukaryotic translation initiation factor 3 complex, eIF3e / positive regulation of mRNA binding ...male germ cell proliferation / translation initiation ternary complex / cap-dependent translational initiation / glial limiting end-foot / viral translational termination-reinitiation / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / negative regulation of translational initiation in response to stress / eukaryotic translation initiation factor 3 complex, eIF3e / positive regulation of mRNA binding / eukaryotic translation initiation factor 3 complex, eIF3m / translation reinitiation / mRNA cap binding / eukaryotic translation initiation factor 2 complex / IRES-dependent viral translational initiation / eukaryotic translation initiation factor 2B complex / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | ||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||||||||
Method | ![]() ![]() ![]() | ||||||||||||
![]() | Thoms, M. / Buschauer, R. / Ameismeier, M. / Denk, T. / Kratzat, H. / Mackens-Kiani, T. / Cheng, J. / Berninghausen, O. / Becker, T. / Beckmann, R. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2. Authors: Matthias Thoms / Robert Buschauer / Michael Ameismeier / Lennart Koepke / Timo Denk / Maximilian Hirschenberger / Hanna Kratzat / Manuel Hayn / Timur Mackens-Kiani / Jingdong Cheng / Jan H ...Authors: 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 / ![]() 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 ...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 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 and various native Nsp1-40 and -80 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. | ||||||||||||
Validation Report | ![]() ![]() ![]() | ||||||||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmcif format | ![]() ![]() ![]() |
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-Related structure data
Related structure data | ![]() 11335CM ![]() 6zlwC ![]() 6zm7C ![]() 6zmeC ![]() 6zmiC ![]() 6zmoC ![]() 6zmtC ![]() 6zn5C ![]() 6zonC C: citing same article ( M: map data used to model this data |
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Similar-shape strucutres |
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Links
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Assembly
Deposited unit | ![]()
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Components
+40S ribosomal protein ... , 31 types, 31 molecules apdQqrstcnmyDzRTwbeuvogkxhPSlij
+Protein/peptide , 1 types, 1 molecules W
+RNA chain , 2 types, 2 molecules 21
+Protein , 4 types, 4 molecules UVXJ
+Eukaryotic translation initiation factor ... , 16 types, 16 molecules GIBACEFHKLMN4OYZ
+Non-polymers , 3 types, 6 molecules 




+Details
-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | ||||||||||||||||||||||||
Vitrification![]() | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() |
Image recording | Electron dose: 44.8 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction![]() | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 53769 / Symmetry type: POINT |