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Open data
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Basic information
| Entry | Database: EMDB / ID: EMD-22681 | |||||||||
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| Title | SARS-COV-2 nsp1 in complex with human 40S ribosome | |||||||||
Map data | composite map | |||||||||
Sample |
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Keywords | nsp1 / 40S / RIBOSOME-VIRAL PROTEIN complex | |||||||||
| Function / homology | Function and homology informationnegative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of ubiquitin-protein transferase activity / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / protein tyrosine kinase inhibitor activity / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of DNA-templated transcription initiation ...negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of ubiquitin-protein transferase activity / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / protein tyrosine kinase inhibitor activity / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of DNA-templated transcription initiation / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / nucleolus organization / TNFR1-mediated ceramide production / negative regulation of RNA splicing / neural crest cell differentiation / supercoiled DNA binding / cytoplasmic translational initiation / NF-kappaB complex / negative regulation of DNA repair / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / rRNA modification in the nucleus and cytosol / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / Formation of the ternary complex, and subsequently, the 43S complex / ion channel inhibitor activity / laminin receptor activity / protein kinase A binding / Ribosomal scanning and start codon recognition / pigmentation / positive regulation of mitochondrial depolarization / Translation initiation complex formation / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / Protein hydroxylation / monocyte chemotaxis / BH3 domain binding / negative regulation of translational frameshifting / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / SARS-CoV-1 modulates host translation machinery / positive regulation of GTPase activity / mTORC1-mediated signalling / TOR signaling / iron-sulfur cluster binding / regulation of cell division / Peptide chain elongation / cellular response to ethanol / Selenocysteine synthesis / Formation of a pool of free 40S subunits / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / negative regulation of protein binding / Eukaryotic Translation Termination / protein serine/threonine kinase inhibitor activity / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / ubiquitin ligase inhibitor activity / negative regulation of respiratory burst involved in inflammatory response / Viral mRNA Translation / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of signal transduction by p53 class mediator / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / negative regulation of ubiquitin-dependent protein catabolic process / 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 / positive regulation of microtubule polymerization / phagocytic cup / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / positive regulation of intrinsic apoptotic signaling pathway / spindle assembly / Protein methylation / translation regulator activity / Nuclear events stimulated by ALK signaling in cancer / 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) / rough endoplasmic reticulum / positive regulation of cell cycle / ribosomal small subunit export from nucleus / laminin binding / translation initiation factor binding / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / gastrulation / DNA-(apurinic or apyrimidinic site) endonuclease activity / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / signaling adaptor activity / Myoclonic epilepsy of Lafora / MDM2/MDM4 family protein binding / FLT3 signaling by CBL mutants / negative regulation of protein ubiquitination / IRAK2 mediated activation of TAK1 complex / Prevention of phagosomal-lysosomal fusion / Alpha-protein kinase 1 signaling pathway Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) / ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
Authors | Wang L / Shi M | |||||||||
Citation | Journal: bioRxiv / Year: 2020Title: SARS-CoV-2 Nsp1 suppresses host but not viral translation through a bipartite mechanism. Authors: Ming Shi / Longfei Wang / Pietro Fontana / Setu Vora / Ying Zhang / Tian-Min Fu / Judy Lieberman / Hao Wu / ![]() Abstract: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly contagious virus that underlies the current COVID-19 pandemic. SARS-CoV-2 is thought to disable various features of host ...The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly contagious virus that underlies the current COVID-19 pandemic. SARS-CoV-2 is thought to disable various features of host immunity and cellular defense. The SARS-CoV-2 nonstructural protein 1 (Nsp1) is known to inhibit host protein translation and could be a target for antiviral therapy against COVID-19. However, how SARS-CoV-2 circumvents this translational blockage for the production of its own proteins is an open question. Here, we report a bipartite mechanism of SARS-CoV-2 Nsp1 which operates by: (1) hijacking the host ribosome via direct interaction of its C-terminal domain (CT) with the 40S ribosomal subunit and (2) specifically lifting this inhibition for SARS-CoV-2 via a direct interaction of its N-terminal domain (NT) with the 5' untranslated region (5' UTR) of SARS-CoV-2 mRNA. We show that while Nsp1-CT is sufficient for binding to 40S and inhibition of host protein translation, the 5' UTR of SARS-CoV-2 mRNA removes this inhibition by binding to Nsp1-NT, suggesting that the Nsp1-NT-UTR interaction is incompatible with the Nsp1-CT-40S interaction. Indeed, lengthening the linker between Nsp1-NT and Nsp1-CT of Nsp1 progressively reduced the ability of SARS-CoV-2 5' UTR to escape the translational inhibition, supporting that the incompatibility is likely steric in nature. The short SL1 region of the 5' UTR is required for viral mRNA translation in the presence of Nsp1. Thus, our data provide a comprehensive view on how Nsp1 switches infected cells from host mRNA translation to SARS-CoV-2 mRNA translation, and that Nsp1 and 5' UTR may be targeted for anti-COVID-19 therapeutics. | |||||||||
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Structure visualization
| Movie |
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| Structure viewer | EM map: SurfView Molmil Jmol/JSmol |
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Downloads & links
-EMDB archive
| Map data | emd_22681.map.gz | 169.6 MB | EMDB map data format | |
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| Header (meta data) | emd-22681-v30.xml emd-22681.xml | 50.4 KB 50.4 KB | Display Display | EMDB header |
| Images | emd_22681.png | 177.1 KB | ||
| Filedesc metadata | emd-22681.cif.gz | 11 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22681 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22681 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 7k5iMC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_22681.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Annotation | composite map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
+Entire : complex of SARS-CoV-2 Nsp1 and human 40S ribosome
+Supramolecule #1: complex of SARS-CoV-2 Nsp1 and human 40S ribosome
+Supramolecule #2: human 40S ribosome
+Supramolecule #3: SARS-CoV-2 Nsp1
+Macromolecule #1: 40S ribosomal protein S17
+Macromolecule #3: 40S ribosomal protein S29
+Macromolecule #4: 40S ribosomal protein S3
+Macromolecule #5: 40S ribosomal protein S5
+Macromolecule #6: 40S ribosomal protein S10
+Macromolecule #7: 40S ribosomal protein S12
+Macromolecule #8: 40S ribosomal protein S15
+Macromolecule #9: 40S ribosomal protein S16
+Macromolecule #10: 40S ribosomal protein S18
+Macromolecule #11: 40S ribosomal protein S19
+Macromolecule #12: 40S ribosomal protein S20
+Macromolecule #13: 40S ribosomal protein S25
+Macromolecule #14: 40S ribosomal protein S28
+Macromolecule #15: 40S ribosomal protein S27a
+Macromolecule #16: Receptor of activated protein C kinase 1
+Macromolecule #17: 40S ribosomal protein SA
+Macromolecule #18: 40S ribosomal protein S3a
+Macromolecule #19: 40S ribosomal protein S2
+Macromolecule #20: 40S ribosomal protein S4, X isoform
+Macromolecule #21: 40S ribosomal protein S6
+Macromolecule #22: 40S ribosomal protein S7
+Macromolecule #23: 40S ribosomal protein S8
+Macromolecule #24: 40S ribosomal protein S9
+Macromolecule #25: 40S ribosomal protein S11
+Macromolecule #26: 40S ribosomal protein S13
+Macromolecule #27: 40S ribosomal protein S14
+Macromolecule #28: 40S ribosomal protein S21
+Macromolecule #29: 40S ribosomal protein S15a
+Macromolecule #30: 40S ribosomal protein S23
+Macromolecule #31: 40S ribosomal protein S24
+Macromolecule #32: 40S ribosomal protein S26
+Macromolecule #33: 40S ribosomal protein S27
+Macromolecule #34: 40S ribosomal protein S30
+Macromolecule #35: 60S ribosomal protein L41
+Macromolecule #36: Host translation inhibitor nsp1
+Macromolecule #2: 40S ribosomal rRNA18S
+Macromolecule #37: MAGNESIUM ION
+Macromolecule #38: ZINC ION
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.4 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | FEI TITAN KRIOS |
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| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
| Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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| Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 794651 |
| Initial angle assignment | Type: ANGULAR RECONSTITUTION |
| Final angle assignment | Type: MAXIMUM LIKELIHOOD |
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About Yorodumi



Keywords
Homo sapiens (human)
Authors
Citation

UCSF Chimera















































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Y (Row.)
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