+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-41039 | |||||||||
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Title | MERS-CoV Nsp1 protein bound to the Human 40S Ribosomal subunit | |||||||||
Map data | Composite Map | |||||||||
Sample |
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Keywords | MERS-CoV Nsp1 / translation inhibition / 40S ribosome / betacoronaviruses / RIBOSOME / Ribosome-Viral Protein complex | |||||||||
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 intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / IRE1-RACK1-PP2A complex ...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 intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / IRE1-RACK1-PP2A complex / nucleolus organization / : / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / laminin receptor activity / oxidized purine DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / neural crest cell differentiation / rRNA modification in the nucleus and cytosol / negative regulation of phagocytosis / NF-kappaB complex / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / pigmentation / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / phagocytic cup / positive regulation of mitochondrial depolarization / negative regulation of Wnt signaling pathway / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / fibroblast growth factor binding / regulation of cell division / SARS-CoV-1 modulates host translation machinery / Protein hydroxylation / iron-sulfur cluster binding / TOR signaling / BH3 domain binding / mTORC1-mediated signalling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Peptide chain elongation / Selenocysteine synthesis / monocyte chemotaxis / cysteine-type endopeptidase activator activity involved in apoptotic process / Formation of a pool of free 40S subunits / ribosomal small subunit export from nucleus / positive regulation of cyclic-nucleotide phosphodiesterase activity / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / translation regulator activity / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / negative regulation of respiratory burst involved in inflammatory response / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / host cell membrane / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol / endoplasmic reticulum-Golgi intermediate compartment / gastrulation / 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 / spindle assembly / regulation of translational fidelity / MDM2/MDM4 family protein binding / laminin binding / Protein methylation / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Nuclear events stimulated by ALK signaling in cancer / negative regulation of smoothened signaling pathway / rescue of stalled ribosome / signaling adaptor activity / positive regulation of cell cycle / negative regulation of peptidyl-serine phosphorylation / stress granule assembly / translation initiation factor binding / maturation of SSU-rRNA / positive regulation of intrinsic apoptotic signaling pathway / Mitotic Prometaphase / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / EML4 and NUDC in mitotic spindle formation / positive regulation of apoptotic signaling pathway / Maturation of protein E Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Middle East respiratory syndrome-related coronavirus | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.6 Å | |||||||||
Authors | Devarkar SC / Xiong Y | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Cell Rep / Year: 2023 Title: Structural basis for translation inhibition by MERS-CoV Nsp1 reveals a conserved mechanism for betacoronaviruses. Authors: Swapnil C Devarkar / Michael Vetick / Shravani Balaji / Ivan B Lomakin / Luojia Yang / Danni Jin / Wendy V Gilbert / Sidi Chen / Yong Xiong / Abstract: All betacoronaviruses (β-CoVs) encode non-structural protein 1 (Nsp1), an essential pathogenicity factor that potently restricts host gene expression. Among the β-CoV family, MERS-CoV is the most ...All betacoronaviruses (β-CoVs) encode non-structural protein 1 (Nsp1), an essential pathogenicity factor that potently restricts host gene expression. Among the β-CoV family, MERS-CoV is the most distantly related member to SARS-CoV-2, and the mechanism for host translation inhibition by MERS-CoV Nsp1 remains controversial. Herein, we show that MERS-CoV Nsp1 directly interacts with the 40S ribosomal subunit. Using cryogenic electron microscopy (cryo-EM), we report a 2.6-Å structure of the MERS-CoV Nsp1 bound to the human 40S ribosomal subunit. The extensive interactions between C-terminal domain of MERS-CoV Nsp1 and the mRNA entry channel of the 40S ribosomal subunit are critical for its translation inhibition function. This mechanism of MERS-CoV Nsp1 is strikingly similar to SARS-CoV and SARS-CoV-2 Nsp1, despite modest sequence conservation. Our results reveal that the mechanism of host translation inhibition is conserved across β-CoVs and highlight a potential therapeutic target for the development of antivirals that broadly restrict β-CoVs. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_41039.map.gz | 100 MB | EMDB map data format | |
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Header (meta data) | emd-41039-v30.xml emd-41039.xml | 54.2 KB 54.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_41039_fsc.xml emd_41039_fsc_2.xml emd_41039_fsc_3.xml | 12.4 KB 12.4 KB 12.4 KB | Display Display Display | FSC data file |
Images | emd_41039.png | 67.1 KB | ||
Filedesc metadata | emd-41039.cif.gz | 11.9 KB | ||
Others | emd_41039_additional_1.map.gz emd_41039_additional_2.map.gz emd_41039_additional_3.map.gz | 106.1 MB 105.9 MB 106 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-41039 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41039 | HTTPS FTP |
-Related structure data
Related structure data | 8t4sMC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_41039.map.gz / Format: CCP4 / Size: 209.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Composite Map | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.07 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: 40S Head subvolume
File | emd_41039_additional_1.map | ||||||||||||
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Annotation | 40S Head subvolume | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Consensus Refinement Map
File | emd_41039_additional_2.map | ||||||||||||
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Annotation | Consensus Refinement Map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: 40S Body subvolume
File | emd_41039_additional_3.map | ||||||||||||
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Annotation | 40S Body subvolume | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : MERS-CoV Nsp1 bound to human 40S ribosomal subunit
+Supramolecule #1: MERS-CoV Nsp1 bound to human 40S ribosomal subunit
+Macromolecule #1: 18S rRNA
+Macromolecule #2: 40S ribosomal protein SA
+Macromolecule #3: 40S ribosomal protein S3a
+Macromolecule #4: 40S ribosomal protein S2
+Macromolecule #5: 40S ribosomal protein S3
+Macromolecule #6: 40S ribosomal protein S4, X isoform
+Macromolecule #7: 40S ribosomal protein S5
+Macromolecule #8: 40S ribosomal protein S6
+Macromolecule #9: 40S ribosomal protein S7
+Macromolecule #10: 40S ribosomal protein S8
+Macromolecule #11: 40S ribosomal protein S9
+Macromolecule #12: 40S ribosomal protein S10
+Macromolecule #13: 40S ribosomal protein S11
+Macromolecule #14: 40S ribosomal protein S12
+Macromolecule #15: 40S ribosomal protein S13
+Macromolecule #16: 40S ribosomal protein S14
+Macromolecule #17: 40S ribosomal protein S15
+Macromolecule #18: 40S ribosomal protein S16
+Macromolecule #19: 40S ribosomal protein S17
+Macromolecule #20: 40S ribosomal protein S18
+Macromolecule #21: 40S ribosomal protein S19
+Macromolecule #22: 40S ribosomal protein S20
+Macromolecule #23: 40S ribosomal protein S21
+Macromolecule #24: 40S ribosomal protein S15a
+Macromolecule #25: 40S ribosomal protein S23
+Macromolecule #26: 40S ribosomal protein S24
+Macromolecule #27: 40S ribosomal protein S25
+Macromolecule #28: 40S ribosomal protein S26
+Macromolecule #29: 40S ribosomal protein S27
+Macromolecule #30: 40S ribosomal protein S28
+Macromolecule #31: 40S ribosomal protein S29
+Macromolecule #32: FAU ubiquitin-like and ribosomal protein S30
+Macromolecule #33: Ubiquitin-40S ribosomal protein S27a
+Macromolecule #34: Receptor of activated protein C kinase 1
+Macromolecule #35: 60S ribosomal protein L41
+Macromolecule #36: Replicase polyprotein 1ab
+Macromolecule #37: MAGNESIUM ION
+Macromolecule #38: ZINC ION
+Macromolecule #39: water
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 81000 |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |