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Yorodumi- EMDB-33993: Cryo-EM density map of EBV gHgL-gp42 in complex with four mAbs 5E... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33993 | |||||||||
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Title | Cryo-EM density map of EBV gHgL-gp42 in complex with four mAbs 5E3, 3E8, 6H2 and 10E4 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | EBV / Cryo-EM / Glycoprotein / gHgL-gp42 complex / Antibody / VIRAL PROTEIN | |||||||||
Biological species | Human gammaherpesvirus 4 (Epstein-Barr virus) / Oryctolagus cuniculus (rabbit) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.59 Å | |||||||||
Authors | Liu L / Sun H / Jiang Y / Liu X / Zhao D / Zheng Q / Li S / Chen Y / Xia N | |||||||||
Funding support | 1 items
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Citation | Journal: Cell Rep Med / Year: 2023 Title: Non-overlapping epitopes on the gHgL-gp42 complex for the rational design of a triple-antibody cocktail against EBV infection. Authors: Junping Hong / Ling Zhong / Liqin Liu / Qian Wu / Wanlin Zhang / Kaiyun Chen / Dongmei Wei / Hui Sun / Xiang Zhou / Xinyu Zhang / Yin-Feng Kang / Yang Huang / Junyu Chen / Guosong Wang / Yan ...Authors: Junping Hong / Ling Zhong / Liqin Liu / Qian Wu / Wanlin Zhang / Kaiyun Chen / Dongmei Wei / Hui Sun / Xiang Zhou / Xinyu Zhang / Yin-Feng Kang / Yang Huang / Junyu Chen / Guosong Wang / Yan Zhou / Yanhong Chen / Qi-Sheng Feng / Hai Yu / Shaowei Li / Mu-Sheng Zeng / Yi-Xin Zeng / Miao Xu / Qingbing Zheng / Yixin Chen / Xiao Zhang / Ningshao Xia / Abstract: Epstein-Barr virus (EBV) is closely associated with cancer, multiple sclerosis, and post-acute coronavirus disease 2019 (COVID-19) sequelae. There are currently no approved therapeutics or vaccines ...Epstein-Barr virus (EBV) is closely associated with cancer, multiple sclerosis, and post-acute coronavirus disease 2019 (COVID-19) sequelae. There are currently no approved therapeutics or vaccines against EBV. It is noteworthy that combining multiple EBV glycoproteins can elicit potent neutralizing antibodies (nAbs) against viral infection, suggesting possible synergistic effects. Here, we characterize three nAbs (anti-gp42 5E3, anti-gHgL 6H2, and anti-gHgL 10E4) targeting different glycoproteins of the gHgL-gp42 complex. Two antibody cocktails synergistically neutralize infection in B cells (5E3+6H2+10E4) and epithelial cells (6H2+10E4) in vitro. Moreover, 5E3 alone and the 5E3+6H2+10E4 cocktail confer potent in vivo protection against lethal EBV challenge in humanized mice. The cryo-EM structure of a heptatomic gHgL-gp42 immune complex reveals non-overlapping epitopes of 5E3, 6H2, and 10E4 on the gHgL-gp42 complex. Structural and functional analyses highlight different neutralization mechanisms for each of the three nAbs. In summary, our results provide insight for the rational design of therapeutics or vaccines against EBV infection. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33993.map.gz | 324 MB | EMDB map data format | |
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Header (meta data) | emd-33993-v30.xml emd-33993.xml | 14.8 KB 14.8 KB | Display Display | EMDB header |
Images | emd_33993.png | 43.8 KB | ||
Filedesc metadata | emd-33993.cif.gz | 3.9 KB | ||
Others | emd_33993_half_map_1.map.gz emd_33993_half_map_2.map.gz | 318 MB 318 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33993 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33993 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_33993.map.gz / Format: CCP4 / Size: 343 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.778 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_33993_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_33993_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : EBV gHgL-gp42 in complex with four mAbs 5E3, 3E8, 6H2 and 10E4
Entire | Name: EBV gHgL-gp42 in complex with four mAbs 5E3, 3E8, 6H2 and 10E4 |
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Components |
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-Supramolecule #1: EBV gHgL-gp42 in complex with four mAbs 5E3, 3E8, 6H2 and 10E4
Supramolecule | Name: EBV gHgL-gp42 in complex with four mAbs 5E3, 3E8, 6H2 and 10E4 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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-Supramolecule #2: gHgL-gp42
Supramolecule | Name: gHgL-gp42 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Human gammaherpesvirus 4 (Epstein-Barr virus) |
-Supramolecule #3: 53E, 3E8, 10E4
Supramolecule | Name: 53E, 3E8, 10E4 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#4 |
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Source (natural) | Organism: Oryctolagus cuniculus (rabbit) |
-Supramolecule #4: 6H2
Supramolecule | Name: 6H2 / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #5 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TECNAI F30 |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Experimental equipment | Model: Tecnai F30 / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.59 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 402382 |