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Open data
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Basic information
Entry | Database: PDB / ID: 6zol | ||||||||||||
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Title | SARS-CoV-2-Nsp1-40S complex, focused on head | ||||||||||||
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![]() | TRANSLATION / inhibitor / mRNA channel / 40S ribosomal subunit | ||||||||||||
Function / homology | ![]() 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 / 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 ...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 / 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 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 / protein kinase A binding / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / pigmentation / 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 / iron-sulfur cluster binding / regulation of cell division / negative regulation of peptidyl-serine phosphorylation / BH3 domain binding / SARS-CoV-1 modulates host translation machinery / 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 / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor 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 / spindle assembly / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of translational fidelity / ribosomal small subunit export from nucleus / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / translation regulator activity / cytosolic ribosome / signaling adaptor activity / negative regulation of smoothened signaling pathway / positive regulation of intrinsic apoptotic signaling pathway / Maturation of protein E / positive regulation of JUN kinase activity / Maturation of protein E / gastrulation / ER Quality Control Compartment (ERQC) / MDM2/MDM4 family protein binding / Myoclonic epilepsy of Lafora / positive regulation of microtubule polymerization / FLT3 signaling by CBL mutants / enzyme activator activity / negative regulation of protein ubiquitination / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / DNA-(apurinic or apyrimidinic site) endonuclease activity / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / 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 / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1-dependent activation of IRF3/IRF7 / Hsp70 protein binding / APC/C:Cdc20 mediated degradation of Cyclin B / translational initiation 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.L. / 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 | ![]() | 614.7 KB | Display | ![]() |
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PDB format | ![]() | 463.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.5 MB | Display | ![]() |
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Full document | ![]() | 1.5 MB | Display | |
Data in XML | ![]() | 72.8 KB | Display | |
Data in CIF | ![]() | 111.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 11322MC ![]() 6zojC ![]() 6zokC 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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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) ![]() |
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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) ![]() 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) ![]() |
#4: Protein | Mass: 18933.846 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#5: Protein | Mass: 14538.987 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#6: Protein | Mass: 17076.207 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#7: Protein | Mass: 16477.377 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#8: Protein | Mass: 15578.156 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#9: Protein | Mass: 17759.777 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Details: P62269 / Source: (natural) ![]() |
#10: Protein | Mass: 16091.562 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#11: Protein | Mass: 13398.763 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#12: Protein | Mass: 13776.224 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#13: Protein | Mass: 6878.940 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
#14: Protein | Mass: 6559.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-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) ![]() |
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#16: Protein | Mass: 34857.355 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Non-polymers , 2 types, 59 molecules ![](data/chem/img/MG.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/ZN.gif)
#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 |
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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: ![]() |
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 |
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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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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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