+Open data
-Basic information
Entry | Database: PDB / ID: 6zol | ||||||||||||
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Title | SARS-CoV-2-Nsp1-40S complex, focused on head | ||||||||||||
Components |
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Keywords | TRANSLATION / inhibitor / mRNA channel / 40S ribosomal subunit | ||||||||||||
Function / homology | Function and homology information 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 / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization ...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 / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / 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 DNA repair / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / oxidized purine DNA binding / supercoiled DNA binding / NF-kappaB complex / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / pigmentation / protein kinase A binding / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / positive regulation of mitochondrial depolarization / 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 / regulation of cell division / iron-sulfur cluster binding / BH3 domain binding / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation / Selenocysteine synthesis / monocyte chemotaxis / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / positive regulation of cyclic-nucleotide phosphodiesterase activity / Eukaryotic Translation Termination / phagocytic cup / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of respiratory burst involved in inflammatory response / 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 / Major pathway of rRNA processing in the nucleolus and cytosol / regulation of translational fidelity / spindle assembly / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / ribosomal small subunit export from nucleus / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / translation regulator activity / negative regulation of smoothened signaling pathway / signaling adaptor activity / negative regulation of peptidyl-serine phosphorylation / positive regulation of intrinsic apoptotic signaling pathway / gastrulation / cytosolic ribosome / Maturation of protein E / positive regulation of JUN kinase activity / Maturation of protein E / positive regulation of microtubule polymerization / MDM2/MDM4 family protein binding / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / negative regulation of protein ubiquitination / Prevention of phagosomal-lysosomal fusion / DNA-(apurinic or apyrimidinic site) endonuclease activity / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / translational initiation / Membrane binding and targetting of GAG proteins / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / Hsp70 protein binding / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||||||||
Authors | Schubert, K. / Karousis, E.D. / Jomaa, A. / Scaiola, A. / Echeverria, B. / Gurzeler, L.-A. / Leibundgut, M.L. / Thiel, V. / Muehlemann, O. / Ban, N. | ||||||||||||
Funding support | Switzerland, 3items
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Citation | Journal: Nat Struct Mol Biol / Year: 2020 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
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6zol.cif.gz | 614.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6zol.ent.gz | 463.8 KB | Display | PDB format |
PDBx/mmJSON format | 6zol.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/zo/6zol ftp://data.pdbj.org/pub/pdb/validation_reports/zo/6zol | HTTPS FTP |
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-Related structure data
Related structure data | 11322MC 6zojC 6zokC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-RNA chain , 1 types, 1 molecules 2
#1: RNA chain | Mass: 602777.875 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
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-40S ribosomal protein ... , 13 types, 13 molecules DFKMPQRSTUZcd
#2: Protein | Mass: 26729.369 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: P23396, DNA-(apurinic or apyrimidinic site) lyase |
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#3: Protein | Mass: 22913.453 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46782 |
#4: Protein | Mass: 18933.846 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P46783 |
#5: Protein | Mass: 14538.987 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P25398 |
#6: Protein | Mass: 17076.207 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62841 |
#7: Protein | Mass: 16477.377 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62249 |
#8: Protein | Mass: 15578.156 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P08708 |
#9: Protein | Mass: 17759.777 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: P62269 / Source: (natural) Homo sapiens (human) / References: UniProt: P62269 |
#10: Protein | Mass: 16091.562 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P39019 |
#11: Protein | Mass: 13398.763 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P60866 |
#12: Protein | Mass: 13776.224 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62851 |
#13: Protein | Mass: 6878.940 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62857 |
#14: Protein | Mass: 6559.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62273 |
-Protein , 2 types, 2 molecules fg
#15: Protein | Mass: 8453.150 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q5RKT7, UniProt: P62979*PLUS |
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#16: Protein | Mass: 34857.355 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P63244 |
-Non-polymers , 2 types, 59 molecules
#17: Chemical | ChemComp-MG / #18: Chemical | |
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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 | Name: SARS-CoV-2-Nsp1-40S complex, focused on head / Type: RIBOSOME / Entity ID: #1-#16 / Source: NATURAL |
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Molecular weight | Units: MEGADALTONS / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.6 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE-PROPANE / Humidity: 100 % / Chamber temperature: 277.15 K |
-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 FIELDBright-field microscopy |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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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 | ||||||||||||||||||||||||
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