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Yorodumi- PDB-6zp4: SARS-CoV-2 Nsp1 bound to a human 43S preinitiation ribosome compl... -
+Open data
-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 | ||||||||||||
Components |
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Keywords | VIRAL PROTEIN / Translational Inhibition / SARS-CoV-2 / Immune Evasion / Human Ribosome | ||||||||||||
Function / homology | Function and homology information male germ cell proliferation / positive regulation of mRNA binding / regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / positive regulation of mRNA cis splicing, via spliceosome / HRI-mediated signaling / response to kainic acid / Cellular response to mitochondrial stress / viral translational termination-reinitiation ...male germ cell proliferation / positive regulation of mRNA binding / regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / positive regulation of mRNA cis splicing, via spliceosome / HRI-mediated signaling / response to kainic acid / Cellular response to mitochondrial stress / 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 / Response of EIF2AK1 (HRI) to heme deficiency / Recycling of eIF2:GDP / cap-dependent translational initiation / eukaryotic translation initiation factor 3 complex, eIF3m / PERK-mediated unfolded protein response / methionyl-initiator methionine tRNA binding / PERK regulates gene expression / IRES-dependent viral translational initiation / translation reinitiation / regulation of translational initiation in response to stress / eukaryotic translation initiation factor 2 complex / eukaryotic translation initiation factor 3 complex / formation of cytoplasmic translation initiation complex / multi-eIF complex / cytoplasmic translational initiation / translation factor activity, RNA binding / protein-synthesizing GTPase / mRNA cap binding / eukaryotic 43S preinitiation complex / formation of translation preinitiation complex / : / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / eukaryotic 48S preinitiation complex / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / supercoiled DNA binding / oxidized purine 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 / positive regulation of ubiquitin-protein transferase activity / negative regulation of phagocytosis / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / cytoplasmic side of rough endoplasmic reticulum membrane / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / laminin receptor activity / pigmentation / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / mammalian oogenesis stage / fibroblast growth factor binding / positive regulation of mitochondrial depolarization / activation-induced cell death of T cells / positive regulation of T cell receptor signaling pathway / negative regulation of peptidyl-serine phosphorylation / iron-sulfur cluster binding / negative regulation of Wnt signaling pathway / positive regulation of activated T cell proliferation / monocyte chemotaxis / Protein hydroxylation / regulation of cell division / BH3 domain binding / cysteine-type endopeptidase activator activity involved in apoptotic process / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / phagocytic cup / ribosomal small subunit binding Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) Severe acute respiratory syndrome coronavirus 2 | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | ||||||||||||
Authors | Thoms, M. / Buschauer, R. / Ameismeier, M. / Denk, T. / Kratzat, H. / Mackens-Kiani, T. / Cheng, J. / Berninghausen, O. / Becker, T. / Beckmann, R. | ||||||||||||
Funding support | Germany, 3items
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Citation | Journal: Science / Year: 2020 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
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6zp4.cif.gz | 2.6 MB | Display | PDBx/mmCIF format |
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PDB format | pdb6zp4.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 6zp4.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6zp4_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 6zp4_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 6zp4_validation.xml.gz | 250.3 KB | Display | |
Data in CIF | 6zp4_validation.cif.gz | 436.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/zp/6zp4 ftp://data.pdbj.org/pub/pdb/validation_reports/zp/6zp4 | HTTPS FTP |
-Related structure data
Related structure data | 11335MC 6zlwC 6zm7C 6zmeC 6zmiC 6zmoC 6zmtC 6zn5C 6zonC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
+40S ribosomal protein ... , 31 types, 31 molecules apdQqrstcnmyDzRTwbeuvogkxhPSlij
-Protein/peptide , 1 types, 1 molecules W
#6: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62945 |
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-RNA chain , 2 types, 2 molecules 21
#18: RNA chain | Mass: 602432.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 337376 |
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#49: RNA chain | Mass: 24215.510 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
-Protein , 4 types, 4 molecules UVXJ
#32: Protein | Mass: 18004.041 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62979 |
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#33: Protein | Mass: 35115.652 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63244 |
#48: Protein | Mass: 5562.077 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
#54: Protein | Mass: 19801.287 Da / Num. of mol.: 1 / Source method: isolated from a natural source Source: (natural) Severe acute respiratory syndrome coronavirus 2 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 ... , 16 types, 16 molecules GIBACEFHKLMN4OYZ
#36: Protein | Mass: 16488.449 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P47813 |
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#37: Protein | Mass: 36543.773 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q13347 |
#38: Protein | Mass: 92593.414 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P55884 |
#39: Protein | Mass: 166903.781 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q14152 |
#40: Protein | Mass: 105503.945 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q99613 |
#41: Protein | Mass: 52281.633 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P60228 |
#42: Protein | Mass: 37593.645 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O00303, ubiquitinyl hydrolase 1 |
#43: Protein | Mass: 39979.277 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O15372 |
#44: Protein | Mass: 25083.619 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9UBQ5 |
#45: Protein | Mass: 66803.734 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9Y262 |
#46: Protein | Mass: 42555.832 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q7L2H7 |
#47: Protein | Mass: 64060.758 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: O15371 |
#50: Protein | Mass: 38454.484 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P20042 |
#51: Protein | Mass: 36161.180 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P05198 |
#52: Protein | Mass: 51178.406 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P41091, protein-synthesizing GTPase |
#53: Protein | Mass: 12752.498 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P41567 |
-Non-polymers , 3 types, 6 molecules
#55: Chemical | ChemComp-ZN / #56: Chemical | ChemComp-GTP / | #57: Chemical | ChemComp-MG / | |
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-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 |
-Sample preparation
Component |
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Source (natural) |
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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 |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 44.8 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-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 |