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- PDB-7yp2: Cryo-EM structure of EBV gHgL-gp42 in complex with mAb 6H2 (local... -

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Basic information

Entry
Database: PDB / ID: 7yp2
TitleCryo-EM structure of EBV gHgL-gp42 in complex with mAb 6H2 (localized refinement)
Components
  • 6H2 heavy chain
  • 6H2 light chain
  • Envelope glycoprotein H
KeywordsVIRAL 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
Herpesvirus glycoprotein H main domain / Herpesvirus glycoprotein H / Herpesvirus glycoprotein H, C-terminal / Herpesvirus glycoprotein H, C-terminal domain superfamily / Herpesvirus glycoprotein H C-terminal domain
Similarity search - Domain/homology
Envelope glycoprotein H
Similarity search - Component
Biological speciesHuman gammaherpesvirus 4 (Epstein-Barr virus)
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.52 Å
AuthorsLiu, L. / Sun, H. / Jiang, Y. / Hong, J. / Zheng, Q. / Li, S. / Chen, Y. / Xia, N.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: 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
DepositionAug 2, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jan 31, 2024Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Envelope glycoprotein H
H: 6H2 heavy chain
L: 6H2 light chain


Theoretical massNumber of molelcules
Total (without water)60,3303
Polymers60,3303
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area4160 Å2
ΔGint-15 kcal/mol
Surface area23990 Å2

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Components

#1: Protein Envelope glycoprotein H / gH


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
#2: Antibody 6H2 heavy chain


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 6H2 light chain


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)

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1EBV gHgL-gp42 in complex with mAb 6H2COMPLEXall0RECOMBINANT
2gHCOMPLEX#11RECOMBINANT
36H2COMPLEX#2-#31RECOMBINANT
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
12Human gammaherpesvirus 4 (Epstein-Barr virus)10376
23Mus musculus (house mouse)10090
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
12Homo sapiens (human)9606
23Homo sapiens (human)9606
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Tecnai F30 / Image courtesy: FEI Company
MicroscopyModel: FEI TECNAI F30
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.52 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 402382 / Symmetry type: POINT

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