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- PDB-6zon: SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome compl... -
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Basic information
Entry | Database: PDB / ID: 6zon | ||||||||||||
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Title | SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome complex - state 1 | ||||||||||||
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![]() | VIRAL PROTEIN / Translational Inhibition / SARS-CoV-2 / Immune Evasion / Human Ribosome | ||||||||||||
Function / homology | ![]() positive regulation of mRNA binding / viral translational termination-reinitiation / eukaryotic translation initiation factor 3 complex, eIF3e / cap-dependent translational initiation / eukaryotic translation initiation factor 3 complex, eIF3m / translation reinitiation / IRES-dependent viral translational initiation / multi-eIF complex / eukaryotic translation initiation factor 3 complex / eukaryotic 43S preinitiation complex ...positive regulation of mRNA binding / viral translational termination-reinitiation / eukaryotic translation initiation factor 3 complex, eIF3e / cap-dependent translational initiation / eukaryotic translation initiation factor 3 complex, eIF3m / translation reinitiation / IRES-dependent viral translational initiation / multi-eIF complex / eukaryotic translation initiation factor 3 complex / eukaryotic 43S preinitiation complex / cytoplasmic translational initiation / mRNA cap binding / formation of cytoplasmic translation initiation complex / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / eukaryotic 48S preinitiation complex / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / IRE1-RACK1-PP2A complex / : / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / metal-dependent deubiquitinase activity / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / oxidized purine DNA binding / supercoiled DNA binding / neural crest cell differentiation / NF-kappaB complex / ubiquitin-like protein conjugating enzyme binding / regulation of translational initiation / regulation of establishment of cell polarity / negative regulation of phagocytosis / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / protein kinase A binding / Translation initiation complex formation / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / ion channel inhibitor activity / pigmentation / mammalian oogenesis stage / positive regulation of mitochondrial depolarization / activation-induced cell death of T cells / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / iron-sulfur cluster binding / protein deubiquitination / regulation of cell division / Protein hydroxylation / negative regulation of peptidyl-serine phosphorylation / BH3 domain binding / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Peptide chain elongation / monocyte chemotaxis / Selenocysteine synthesis / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / Formation of a pool of free 40S subunits / phagocytic cup / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of respiratory burst involved in inflammatory response / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Viral mRNA Translation / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / L13a-mediated translational silencing of Ceruloplasmin expression / GTP hydrolysis and joining of the 60S ribosomal subunit / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / TOR signaling / T cell proliferation involved in immune response / Major pathway of rRNA processing in the nucleolus and cytosol / spindle assembly / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of translational fidelity / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / ribosomal small subunit export from nucleus / erythrocyte development / translation regulator activity / Protein methylation Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | ||||||||||||
![]() | 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. | ||||||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 2.4 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.3 MB | Display | |
Data in XML | ![]() | 231.8 KB | Display | |
Data in CIF | ![]() | 402.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 11325MC ![]() 6zlwC ![]() 6zm7C ![]() 6zmeC ![]() 6zmiC ![]() 6zmoC ![]() 6zmtC ![]() 6zn5C ![]() 6zp4C C: citing same article ( M: map data used to model this data |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
+40S ribosomal protein ... , 31 types, 31 molecules apdQqrstcnmiyfjzRTwgbeuvokxhPSl
-Protein , 4 types, 4 molecules UVYJ
#34: Protein | Mass: 18004.041 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 / Source: (gene. exp.) ![]() ![]() ![]() |
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#35: Protein | Mass: 35115.652 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 / Source: (gene. exp.) ![]() ![]() ![]() |
#47: Protein | Mass: 6656.196 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 / Source: (gene. exp.) ![]() ![]() ![]() |
#48: Protein | Mass: 19801.287 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 Source: (gene. exp.) ![]() ![]() Description: sample / Production host: ![]() ![]() References: UniProt: P0DTD1, ubiquitinyl hydrolase 1, Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases, SARS coronavirus main proteinase, RNA-directed RNA polymerase, DNA ...References: UniProt: P0DTD1, ubiquitinyl hydrolase 1, Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases, SARS coronavirus main proteinase, RNA-directed RNA polymerase, DNA helicase, RNA helicase, Hydrolases; Acting on ester bonds; Exoribonucleases producing 5'-phosphomonoesters, Hydrolases; Acting on ester bonds, Transferases; Transferring one-carbon groups; Methyltransferases |
-Eukaryotic translation initiation factor 3 subunit ... , 11 types, 11 molecules IBACEFHKLMD
#36: Protein | Mass: 36543.773 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 / Source: (gene. exp.) ![]() ![]() ![]() |
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#37: Protein | Mass: 92593.414 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 / Source: (gene. exp.) ![]() ![]() ![]() |
#38: Protein | Mass: 79249.359 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1, 602 / Source: (gene. exp.) ![]() ![]() ![]() |
#39: Protein | Mass: 105503.945 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 / Source: (gene. exp.) ![]() ![]() ![]() |
#40: Protein | Mass: 52281.633 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 / Source: (gene. exp.) ![]() ![]() ![]() |
#41: Protein | Mass: 37593.645 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 / Source: (gene. exp.) ![]() ![]() ![]() |
#42: Protein | Mass: 39979.277 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 / Source: (gene. exp.) ![]() ![]() ![]() |
#43: Protein | Mass: 25083.619 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 / Source: (gene. exp.) ![]() ![]() ![]() |
#44: Protein | Mass: 66803.734 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 / Source: (gene. exp.) ![]() ![]() ![]() |
#45: Protein | Mass: 42555.832 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 / Source: (gene. exp.) ![]() ![]() ![]() |
#46: Protein | Mass: 64060.758 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 / Source: (gene. exp.) ![]() ![]() ![]() |
-Protein/peptide / RNA chain / Non-polymers , 3 types, 5 molecules W2![](data/chem/img/ZN.gif)
![](data/chem/img/ZN.gif)
#20: RNA chain | Mass: 602432.625 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 / Source: (gene. exp.) ![]() ![]() ![]() | ||
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#49: Chemical | #6: Protein/peptide | | Mass: 3473.451 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 1 / Source: (gene. exp.) ![]() ![]() ![]() |
-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
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: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 13928 / Symmetry type: POINT |