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Yorodumi- EMDB-6794: Cryo-EM structure of zika virus complexed with Fab of a human mon... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-6794 | |||||||||
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Title | Cryo-EM structure of zika virus complexed with Fab of a human monoclonal antibody named ZKA190 at 4 degrees celsius | |||||||||
Map data | zika virus complexed with Fab of a human monoclonal antibody named ZKA190 at 4 celsius degree | |||||||||
Sample |
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Biological species | Zika virus / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 22.0 Å | |||||||||
Authors | Wang JQ / Ng TS / Fibriansah G / Lok SM | |||||||||
Citation | Journal: Cell / Year: 2017 Title: A Human Bi-specific Antibody against Zika Virus with High Therapeutic Potential. Authors: Jiaqi Wang / Marco Bardelli / Diego A Espinosa / Mattia Pedotti / Thiam-Seng Ng / Siro Bianchi / Luca Simonelli / Elisa X Y Lim / Mathilde Foglierini / Fabrizia Zatta / Stefano Jaconi / ...Authors: Jiaqi Wang / Marco Bardelli / Diego A Espinosa / Mattia Pedotti / Thiam-Seng Ng / Siro Bianchi / Luca Simonelli / Elisa X Y Lim / Mathilde Foglierini / Fabrizia Zatta / Stefano Jaconi / Martina Beltramello / Elisabetta Cameroni / Guntur Fibriansah / Jian Shi / Taylor Barca / Isabel Pagani / Alicia Rubio / Vania Broccoli / Elisa Vicenzi / Victoria Graham / Steven Pullan / Stuart Dowall / Roger Hewson / Simon Jurt / Oliver Zerbe / Karin Stettler / Antonio Lanzavecchia / Federica Sallusto / Andrea Cavalli / Eva Harris / Shee-Mei Lok / Luca Varani / Davide Corti / Abstract: Zika virus (ZIKV), a mosquito-borne flavivirus, causes devastating congenital birth defects. We isolated a human monoclonal antibody (mAb), ZKA190, that potently cross-neutralizes multi-lineage ZIKV ...Zika virus (ZIKV), a mosquito-borne flavivirus, causes devastating congenital birth defects. We isolated a human monoclonal antibody (mAb), ZKA190, that potently cross-neutralizes multi-lineage ZIKV strains. ZKA190 is highly effective in vivo in preventing morbidity and mortality of ZIKV-infected mice. NMR and cryo-electron microscopy show its binding to an exposed epitope on DIII of the E protein. ZKA190 Fab binds all 180 E protein copies, altering the virus quaternary arrangement and surface curvature. However, ZIKV escape mutants emerged in vitro and in vivo in the presence of ZKA190, as well as of other neutralizing mAbs. To counter this problem, we developed a bispecific antibody (FIT-1) comprising ZKA190 and a second mAb specific for DII of E protein. In addition to retaining high in vitro and in vivo potencies, FIT-1 robustly prevented viral escape, warranting its development as a ZIKV immunotherapy. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_6794.map.gz | 27.2 MB | EMDB map data format | |
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Header (meta data) | emd-6794-v30.xml emd-6794.xml | 12.1 KB 12.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_6794_fsc.xml | 6.7 KB | Display | FSC data file |
Images | emd_6794.png | 180.2 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-6794 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-6794 | HTTPS FTP |
-Validation report
Summary document | emd_6794_validation.pdf.gz | 78.8 KB | Display | EMDB validaton report |
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Full document | emd_6794_full_validation.pdf.gz | 77.9 KB | Display | |
Data in XML | emd_6794_validation.xml.gz | 494 B | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-6794 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-6794 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_6794.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | zika virus complexed with Fab of a human monoclonal antibody named ZKA190 at 4 celsius degree | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 3.42 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : zika virus complexed with Fab molecule of a human monoclonal anti...
Entire | Name: zika virus complexed with Fab molecule of a human monoclonal antibody named ZKA190 |
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Components |
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-Supramolecule #1: zika virus complexed with Fab molecule of a human monoclonal anti...
Supramolecule | Name: zika virus complexed with Fab molecule of a human monoclonal antibody named ZKA190 type: complex / ID: 1 / Parent: 0 |
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Source (natural) | Organism: Zika virus / Strain: H/PF/2013 |
-Supramolecule #2: zika virus
Supramolecule | Name: zika virus / type: complex / ID: 2 / Parent: 1 |
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Source (natural) | Organism: Zika virus / Strain: H/PF/2013 |
-Supramolecule #3: Fab ZKA190
Supramolecule | Name: Fab ZKA190 / type: complex / ID: 3 / Parent: 1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: EXPI293 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1 mg/mL | ||||||||
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Buffer | pH: 8 Component:
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Grid | Material: COPPER / Support film - Material: CARBON / Support film - topology: LACEY / Pretreatment - Type: GLOW DISCHARGE | ||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON II (4k x 4k) / Average electron dose: 20.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |