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- PDB-7yoy: Cryo-EM structure of EBV gHgL-gp42 in complex with mAbs 3E8 and 5... -

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Basic information

Entry
Database: PDB / ID: 7yoy
TitleCryo-EM structure of EBV gHgL-gp42 in complex with mAbs 3E8 and 5E3 (localized refinement)
Components
  • 3E8 heavy chain
  • 3E8 light chain
  • 5E3 heavy chain
  • 5E3 light chain
  • Soluble gp42
KeywordsVIRAL PROTEIN / EBV / Cryo-EM / Glycoprotein / gHgL-gp42 complex / Antibody
Function / homologyC-type lectin-like/link domain superfamily / C-type lectin fold / carbohydrate binding / virion membrane / membrane / Glycoprotein 42
Function and homology information
Biological speciesHuman gammaherpesvirus 4 (Epstein-Barr virus)
Oryctolagus cuniculus (rabbit)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.64 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

Downloads & links

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Assembly

Deposited unit
C: Soluble gp42
E: 5E3 heavy chain
F: 3E8 heavy chain
I: 5E3 light chain
J: 3E8 light chain


Theoretical massNumber of molelcules
Total (without water)64,2495
Polymers64,2495
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area6890 Å2
ΔGint-36 kcal/mol
Surface area27100 Å2

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Components

#1: Protein Soluble gp42


Mass: 15593.692 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: BZLF2 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P0C6Z5
#2: Protein 5E3 heavy chain


Mass: 13153.532 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Oryctolagus cuniculus (rabbit) / Cell line (production host): HEK293 / Production host: Homo sapiens (human)
#3: Protein 3E8 heavy chain


Mass: 12123.596 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Oryctolagus cuniculus (rabbit) / Cell line (production host): HEK293 / Production host: Homo sapiens (human)
#4: Antibody 5E3 light chain


Mass: 11543.807 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Oryctolagus cuniculus (rabbit) / Cell line (production host): HEK293 / Production host: Homo sapiens (human)
#5: Antibody 3E8 light chain


Mass: 11834.026 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Oryctolagus cuniculus (rabbit) / 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 mAbs 3E8 and 5E3COMPLEXall0RECOMBINANT
2gp42COMPLEX#11RECOMBINANT
35E3,3E8COMPLEX#2-#51RECOMBINANT
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
12Human gammaherpesvirus 4 (Epstein-Barr virus)10376
23Oryctolagus cuniculus (rabbit)9986
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 FIELD / 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: 3.64 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 167595 / Symmetry type: POINT

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