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Yorodumi- PDB-7yp2: Cryo-EM structure of EBV gHgL-gp42 in complex with mAb 6H2 (local... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7yp2 | ||||||
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Title | Cryo-EM structure of EBV gHgL-gp42 in complex with mAb 6H2 (localized refinement) | ||||||
Components |
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Keywords | VIRAL PROTEIN / EBV / Cryo-EM / Glycoprotein / gHgL-gp42 complex / Antibody | ||||||
Function / homology | Function and homology information host cell endosome membrane / symbiont entry into host cell / fusion of virus membrane with host plasma membrane / viral envelope / host cell plasma membrane / virion membrane / membrane Similarity search - Function | ||||||
Biological species | Human gammaherpesvirus 4 (Epstein-Barr virus) Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.52 Å | ||||||
Authors | Liu, L. / Sun, H. / Jiang, Y. / Hong, J. / Zheng, Q. / Li, S. / Chen, Y. / Xia, N. | ||||||
Funding support | 1items
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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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7yp2.cif.gz | 104 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7yp2.ent.gz | 79.8 KB | Display | PDB format |
PDBx/mmJSON format | 7yp2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7yp2_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 7yp2_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 7yp2_validation.xml.gz | 31.5 KB | Display | |
Data in CIF | 7yp2_validation.cif.gz | 43.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yp/7yp2 ftp://data.pdbj.org/pub/pdb/validation_reports/yp/7yp2 | HTTPS FTP |
-Related structure data
Related structure data | 33994MC 7yoyC 7yp1C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 34794.770 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human gammaherpesvirus 4 (Epstein-Barr virus) Strain: GD1 / Gene: gH / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: A0A385J8N2 |
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#2: Antibody | Mass: 13220.722 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) |
#3: Antibody | Mass: 12314.811 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Tecnai F30 / Image courtesy: FEI Company |
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Microscopy | Model: FEI TECNAI F30 |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.52 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 402382 / Symmetry type: POINT |