+
Open data
-
Basic information
| Entry | Database: EMDB / ID: EMD-22681 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Title | SARS-COV-2 nsp1 in complex with human 40S ribosome | |||||||||
Map data | composite map | |||||||||
Sample |
| |||||||||
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 respiratory burst involved in inflammatory response / positive regulation of gastrulation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / protein tyrosine kinase inhibitor activity / nucleolus organization / positive regulation of ubiquitin-protein transferase activity ...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 respiratory burst involved in inflammatory response / positive regulation of gastrulation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / protein tyrosine kinase inhibitor activity / nucleolus organization / positive regulation of ubiquitin-protein transferase activity / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / positive regulation of DNA-templated transcription initiation / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / supercoiled DNA binding / NF-kappaB complex / cysteine-type endopeptidase activator activity involved in apoptotic process / cytoplasmic translational initiation / neural crest cell differentiation / oxidized purine DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of bicellular tight junction assembly / regulation of establishment of cell polarity / ubiquitin-like protein conjugating enzyme binding / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / negative regulation of phagocytosis / Formation of the ternary complex, and subsequently, the 43S complex / cytoplasmic side of rough endoplasmic reticulum membrane / protein kinase A binding / ion channel inhibitor activity / laminin receptor activity / Ribosomal scanning and start codon recognition / pigmentation / Translation initiation complex formation / positive regulation of mitochondrial depolarization / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / monocyte chemotaxis / negative regulation of translational frameshifting / TOR signaling / BH3 domain binding / Protein hydroxylation / SARS-CoV-1 modulates host translation machinery / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / iron-sulfur cluster binding / mTORC1-mediated signalling / regulation of cell division / Peptide chain elongation / positive regulation of GTPase activity / 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 / Eukaryotic Translation Termination / protein serine/threonine kinase inhibitor activity / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / negative regulation of ubiquitin-dependent protein catabolic process / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Viral mRNA Translation / negative regulation of respiratory burst involved in inflammatory response / ubiquitin ligase inhibitor activity / negative regulation of protein binding / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / positive regulation of signal transduction by p53 class mediator / 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 / phagocytic cup / positive regulation of microtubule polymerization / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / positive regulation of intrinsic apoptotic signaling pathway / spindle assembly / Protein methylation / 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) / Nuclear events stimulated by ALK signaling in cancer / translation regulator activity / positive regulation of cell cycle / rough endoplasmic reticulum / laminin binding / ribosomal small subunit export from nucleus / translation initiation factor binding / Maturation of protein E / Maturation of protein E / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / DNA-(apurinic or apyrimidinic site) endonuclease activity / gastrulation / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / signaling adaptor activity / IRAK2 mediated activation of TAK1 complex / Prevention of phagosomal-lysosomal fusion / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex 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. | |||||||||
| History |
|
-
Structure visualization
| Movie |
Movie viewer |
|---|---|
| Structure viewer | EM map: SurfView Molmil Jmol/JSmol |
| Supplemental images |
-
Downloads & links
-EMDB archive
| Map data | emd_22681.map.gz | 169.6 MB | EMDB map data format | |
|---|---|---|---|---|
| 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 ( |
|---|---|
| Similar structure data |
-
Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
|---|---|
| Related items in Molecule of the Month |
-
Map
| File | Download / File: emd_22681.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Annotation | composite map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
CCP4 map header:
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
-Supplemental data
-
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 |
|---|---|
Processing | single particle reconstruction |
| Aggregation state | particle |
-
Sample preparation
| Buffer | pH: 7.4 |
|---|---|
| Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
| Microscope | FEI TITAN KRIOS |
|---|---|
| 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 |
-
Image processing
| Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
|---|---|
| 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 |
Movie
Controller
About Yorodumi



Keywords
Homo sapiens (human)
Authors
Citation

UCSF Chimera















































Z (Sec.)
Y (Row.)
X (Col.)
























