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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 | ![]() oxidized pyrimidine DNA binding / response to TNF agonist / negative regulation of endoplasmic reticulum unfolded protein response / positive regulation of base-excision repair / 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 / protein tyrosine kinase inhibitor activity / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity ...oxidized pyrimidine DNA binding / response to TNF agonist / negative regulation of endoplasmic reticulum unfolded protein response / positive regulation of base-excision repair / 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 / protein tyrosine kinase inhibitor activity / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / nucleolus organization / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of DNA repair / supercoiled DNA binding / NF-kappaB complex / cysteine-type endopeptidase activator activity involved in apoptotic process / oxidized purine DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / regulation of establishment of cell polarity / ubiquitin-like protein conjugating enzyme binding / 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 / ion channel inhibitor activity / Ribosomal scanning and start codon recognition / pigmentation / Translation initiation complex formation / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / monocyte chemotaxis / positive regulation of activated T cell proliferation / negative regulation of translational frameshifting / BH3 domain binding / SARS-CoV-1 modulates host translation machinery / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / regulation of cell division / iron-sulfur cluster binding / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / Eukaryotic Translation Termination / ubiquitin ligase inhibitor activity / positive regulation of GTPase activity / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / positive regulation of signal transduction by p53 class mediator / protein serine/threonine kinase inhibitor activity / Viral mRNA Translation / negative regulation of respiratory burst involved in inflammatory response / 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 / phagocytic cup / regulation of translational fidelity / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / negative regulation of protein binding / spindle assembly / positive regulation of intrinsic apoptotic signaling pathway / ribosomal small subunit export from nucleus / translation regulator activity / gastrulation / Maturation of protein E / signaling adaptor activity / Maturation of protein E / DNA-(apurinic or apyrimidinic site) endonuclease activity / positive regulation of microtubule polymerization / MDM2/MDM4 family protein binding / ER Quality Control Compartment (ERQC) / Hsp70 protein binding / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / negative regulation of protein ubiquitination / Prevention of phagosomal-lysosomal fusion / 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 / Endosomal Sorting Complex Required For Transport (ESCRT) / Membrane binding and targetting of GAG proteins / liver regeneration / Negative regulation of FLT3 / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Constitutive Signaling by NOTCH1 HD Domain Mutants / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / NOTCH2 Activation and Transmission of Signal to the Nucleus / cytosolic ribosome / positive regulation of interleukin-2 production / TICAM1,TRAF6-dependent induction of TAK1 complex / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / class I DNA-(apurinic or apyrimidinic site) endonuclease activity 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 | ![]() | 615.3 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 | ![]() | 73.3 KB | Display | |
Data in CIF | ![]() | 113.8 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 


#17: Chemical | ChemComp-MG / #18: Chemical | |
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-Details
Has ligand of interest | N |
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Has protein modification | N |
-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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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 | ||||||||||||||||||||||||
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