+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-40310 | |||||||||
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Title | BtCoV-422 spike in complex with JC57-11 Fab, local map | |||||||||
Map data | BtCoV-422 spike in complex with JC57-11 Fab, local sharpened map | |||||||||
Sample |
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Keywords | coronavirus / MERS / neutralizing / antibody / MERS-like / merbecovirus / bat / virus / CDRH3 / RBD / VIRAL PROTEIN | |||||||||
Biological species | Middle East respiratory syndrome-related coronavirus / Macaca (macaques) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | McFadden E / McLellan JS | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Sci Transl Med / Year: 2023 Title: A MERS-CoV antibody neutralizes a pre-emerging group 2c bat coronavirus. Authors: Longping V Tse / Yixuan J Hou / Elizabeth McFadden / Rhianna E Lee / Trevor D Scobey / Sarah R Leist / David R Martinez / Rita M Meganck / Alexandra Schäfer / Boyd L Yount / Teresa Mascenik ...Authors: Longping V Tse / Yixuan J Hou / Elizabeth McFadden / Rhianna E Lee / Trevor D Scobey / Sarah R Leist / David R Martinez / Rita M Meganck / Alexandra Schäfer / Boyd L Yount / Teresa Mascenik / John M Powers / Scott H Randell / Yi Zhang / Lingshu Wang / John Mascola / Jason S McLellan / Ralph S Baric / Abstract: The repeated emergence of zoonotic human betacoronaviruses (β-CoVs) dictates the need for broad therapeutics and conserved epitope targets for countermeasure design. Middle East respiratory syndrome ...The repeated emergence of zoonotic human betacoronaviruses (β-CoVs) dictates the need for broad therapeutics and conserved epitope targets for countermeasure design. Middle East respiratory syndrome (MERS)-related coronaviruses (CoVs) remain a pressing concern for global health preparedness. Using metagenomic sequence data and CoV reverse genetics, we recovered a full-length wild-type MERS-like BtCoV//GD/2014-422 (BtCoV-422) recombinant virus, as well as two reporter viruses, and evaluated their human emergence potential and susceptibility to currently available countermeasures. Similar to MERS-CoV, BtCoV-422 efficiently used human and other mammalian dipeptidyl peptidase protein 4 (DPP4) proteins as entry receptors and an alternative DPP4-independent infection route in the presence of exogenous proteases. BtCoV-422 also replicated efficiently in primary human airway, lung endothelial, and fibroblast cells, although less efficiently than MERS-CoV. However, BtCoV-422 shows minor signs of infection in 288/330 human DPP4 transgenic mice. Several broad CoV antivirals, including nucleoside analogs and 3C-like/M protease inhibitors, demonstrated potent inhibition against BtCoV-422 in vitro. Serum from mice that received a MERS-CoV mRNA vaccine showed reduced neutralizing activity against BtCoV-422. Although most MERS-CoV-neutralizing monoclonal antibodies (mAbs) had limited activity, one anti-MERS receptor binding domain mAb, JC57-11, neutralized BtCoV-422 potently. A cryo-electron microscopy structure of JC57-11 in complex with BtCoV-422 spike protein revealed the mechanism of cross-neutralization involving occlusion of the DPP4 binding site, highlighting its potential as a broadly neutralizing mAb for group 2c CoVs that use DPP4 as a receptor. These studies provide critical insights into MERS-like CoVs and provide candidates for countermeasure development. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_40310.map.gz | 230.3 MB | EMDB map data format | |
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Header (meta data) | emd-40310-v30.xml emd-40310.xml | 18.6 KB 18.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_40310_fsc.xml | 13.2 KB | Display | FSC data file |
Images | emd_40310.png | 51.4 KB | ||
Filedesc metadata | emd-40310.cif.gz | 4.4 KB | ||
Others | emd_40310_additional_1.map.gz emd_40310_additional_2.map.gz emd_40310_half_map_1.map.gz emd_40310_half_map_2.map.gz | 122.2 MB 203 MB 226.6 MB 226.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-40310 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40310 | HTTPS FTP |
-Validation report
Summary document | emd_40310_validation.pdf.gz | 1.2 MB | Display | EMDB validaton report |
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Full document | emd_40310_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | emd_40310_validation.xml.gz | 21.2 KB | Display | |
Data in CIF | emd_40310_validation.cif.gz | 26.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40310 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40310 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_40310.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | BtCoV-422 spike in complex with JC57-11 Fab, local sharpened map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.8332 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: BtCoV-422 spike in complex with JC57-11 Fab, local unsharpened map
File | emd_40310_additional_1.map | ||||||||||||
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Annotation | BtCoV-422 spike in complex with JC57-11 Fab, local unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: BtCoV-422 spike in complex with JC57-11 Fab, local...
File | emd_40310_additional_2.map | ||||||||||||
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Annotation | BtCoV-422 spike in complex with JC57-11 Fab, local DeepEMhanced map used for generation of composite map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: BtCoV-422 spike in complex with JC57-11 Fab, local half map A
File | emd_40310_half_map_1.map | ||||||||||||
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Annotation | BtCoV-422 spike in complex with JC57-11 Fab, local half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: BtCoV-422 spike in complex with JC57-11 Fab, local half map B
File | emd_40310_half_map_2.map | ||||||||||||
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Annotation | BtCoV-422 spike in complex with JC57-11 Fab, local half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : btCoV-422 in complex with JC57-11 Fab
Entire | Name: btCoV-422 in complex with JC57-11 Fab |
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Components |
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-Supramolecule #1: btCoV-422 in complex with JC57-11 Fab
Supramolecule | Name: btCoV-422 in complex with JC57-11 Fab / type: complex / ID: 1 / Parent: 0 |
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Molecular weight | Theoretical: 650 KDa |
-Supramolecule #2: BtCoV-422 spike
Supramolecule | Name: BtCoV-422 spike / type: complex / ID: 2 / Parent: 1 |
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Source (natural) | Organism: Middle East respiratory syndrome-related coronavirus |
Molecular weight | Theoretical: 600 KDa |
-Supramolecule #3: JC57-11 Fab
Supramolecule | Name: JC57-11 Fab / type: complex / ID: 3 / Parent: 1 |
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Source (natural) | Organism: Macaca (macaques) |
Molecular weight | Theoretical: 50 KDa |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 80.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: DIFFRACTION / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |