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Open data
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Basic information
Entry | Database: PDB / ID: 6zok | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Title | SARS-CoV-2-Nsp1-40S complex, focused on body | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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![]() | TRANSLATION / inhibitor / mRNA channel / 40S ribosomal subunit | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Function / homology | ![]() translation at postsynapse / negative regulation of RNA splicing / mammalian oogenesis stage / activation-induced cell death of T cells / neural crest cell differentiation / translation at presynapse / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / rRNA modification in the nucleus and cytosol ...translation at postsynapse / negative regulation of RNA splicing / mammalian oogenesis stage / activation-induced cell death of T cells / neural crest cell differentiation / translation at presynapse / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / rRNA modification in the nucleus and cytosol / laminin receptor activity / cytoplasmic side of rough endoplasmic reticulum membrane / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / Translation initiation complex formation / fibroblast growth factor binding / Protein hydroxylation / TOR signaling / SARS-CoV-1 modulates host translation machinery / mTORC1-mediated signalling / Peptide chain elongation / T cell proliferation involved in immune response / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Selenocysteine synthesis / Formation of a pool of free 40S subunits / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of ubiquitin-dependent protein catabolic process / Viral mRNA Translation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / erythrocyte development / Major pathway of rRNA processing in the nucleolus and cytosol / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Protein methylation / Nuclear events stimulated by ALK signaling in cancer / laminin binding / rough endoplasmic reticulum / translation regulator activity / positive regulation of cell cycle / translation initiation factor binding / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / gastrulation / cytosolic ribosome / antiviral innate immune response / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / stress granule assembly / Resolution of Sister Chromatid Cohesion / innate immune response in mucosa / erythrocyte differentiation / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of translation / mRNA 3'-UTR binding / maturation of SSU-rRNA / neural tube closure / translational initiation / small-subunit processome / placenta development / RHO GTPases Activate Formins / maintenance of translational fidelity / response to virus / modification-dependent protein catabolic process / mRNA 5'-UTR binding / G1/S transition of mitotic cell cycle / RMTs methylate histone arginines / Regulation of expression of SLITs and ROBOs / protein tag activity / cytoplasmic ribonucleoprotein granule / antimicrobial humoral immune response mediated by antimicrobial peptide / rRNA processing / Separation of Sister Chromatids / antibacterial humoral response / glucose homeostasis / protein guanylyltransferase activity / RNA endonuclease activity producing 3'-phosphomonoesters, hydrolytic mechanism / presynapse / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / ribosome binding / Lyases; Phosphorus-oxygen lyases / T cell differentiation in thymus / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / virus receptor activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / Maturation of replicase proteins / cell body / ribosomal small subunit biogenesis / ISG15-specific peptidase activity / ribosomal small subunit assembly / TRAF3-dependent IRF activation pathway / Transcription of SARS-CoV-2 sgRNAs / snRNP Assembly / Translation of Replicase and Assembly of the Replication Transcription Complex / small ribosomal subunit Similarity search - Function | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
![]() | Schubert, K. / Karousis, E.D. / Jomaa, A. / Scaiola, A. / Echeverria, B. / Gurzeler, L.-A. / Leibundgut, M. / Thiel, V. / Muehlemann, O. / Ban, N. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation. Authors: Katharina Schubert / Evangelos D Karousis / Ahmad Jomaa / Alain Scaiola / Blanca Echeverria / Lukas-Adrian Gurzeler / Marc Leibundgut / Volker Thiel / Oliver Mühlemann / Nenad Ban / ![]() Abstract: The SARS-CoV-2 non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, suppresses host innate immune functions. By combining cryo-electron microscopy and biochemistry, we show ...The SARS-CoV-2 non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, suppresses host innate immune functions. By combining cryo-electron microscopy and biochemistry, we show that SARS-CoV-2 Nsp1 binds to the human 40S subunit in ribosomal complexes, including the 43S pre-initiation complex and the non-translating 80S ribosome. The protein inserts its C-terminal domain into the mRNA channel, where it interferes with mRNA binding. We observe translation inhibition in the presence of Nsp1 in an in vitro translation system and in human cells. Based on the high-resolution structure of the 40S-Nsp1 complex, we identify residues of Nsp1 crucial for mediating translation inhibition. We further show that the full-length 5' untranslated region of the genomic viral mRNA stimulates translation in vitro, suggesting that SARS-CoV-2 combines global inhibition of translation by Nsp1 with efficient translation of the viral mRNA to allow expression of viral genes. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1.1 MB | Display | ![]() |
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PDB format | ![]() | 876.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.5 MB | Display | ![]() |
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Full document | ![]() | 1.6 MB | Display | |
Data in XML | ![]() | 106.1 KB | Display | |
Data in CIF | ![]() | 172.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 11321MC ![]() 6zojC ![]() 6zolC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-40S ribosomal protein ... , 19 types, 19 molecules ABCEGHIJLNORVWXYabe
#2: Protein | Mass: 32883.938 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#3: Protein | Mass: 30002.061 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#4: Protein | Mass: 31376.516 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#5: Protein | Mass: 29654.869 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#6: Protein | Mass: 28751.906 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#7: Protein | Mass: 22168.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#8: Protein | Mass: 24263.387 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#9: Protein | Mass: 22641.564 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#10: Protein | Mass: 18468.826 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#11: Protein | Mass: 17259.389 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#12: Protein | Mass: 16302.772 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#13: Protein | Mass: 15578.156 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#14: Protein | Mass: 9124.389 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#15: Protein | Mass: 14865.555 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#16: Protein | Mass: 15844.666 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#17: Protein | Mass: 15107.924 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#18: Protein | Mass: 11645.794 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#19: Protein | Mass: 9210.843 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#20: Protein | Mass: 6302.480 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-RNA chain / Protein / Protein/peptide , 3 types, 3 molecules 2jh
#1: RNA chain | Mass: 602777.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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#21: Protein | Mass: 19801.287 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Gene: rep, 1a-1b / 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 |
#22: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Non-polymers , 2 types, 110 molecules 


#23: Chemical | ChemComp-MG / #24: Chemical | ChemComp-ZN / | |
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-Details
Has ligand of interest | N |
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Has protein modification | Y |
-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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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||||||||||
Buffer solution | pH: 7.6 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE-PROPANE |
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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: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 118765 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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