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- PDB-7yp1: Cryo-EM structure of EBV gHgL-gp42 in complex with mAb 10E4 (loca... -

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Basic information

Entry
Database: PDB / ID: 7yp1
TitleCryo-EM structure of EBV gHgL-gp42 in complex with mAb 10E4 (localized refinement)
Components
  • 10E4 heavy chain
  • 10E4 light chain
  • EBV gH
  • EBV gL
KeywordsVIRAL PROTEIN / EBV / Cryo-EM / Glycoprotein / gHgL-gp42 complex / Antibody
Biological speciesHuman gammaherpesvirus 4 (Epstein-Barr virus)
Oryctolagus cuniculus (rabbit)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.54 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: EBV gH
B: EBV gL
D: 10E4 heavy chain
G: 10E4 light chain


Theoretical massNumber of molelcules
Total (without water)55,5894
Polymers55,5894
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein EBV gH


Mass: 22774.117 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human gammaherpesvirus 4 (Epstein-Barr virus)
Cell line (production host): HEK293 / Production host: Homo sapiens (human)
#2: Protein EBV gL


Mass: 8623.719 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human gammaherpesvirus 4 (Epstein-Barr virus)
Cell line (production host): HEK293 / Production host: Homo sapiens (human)
#3: Protein 10E4 heavy chain


Mass: 12273.763 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 10E4 light chain


Mass: 11917.251 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
1gHgL-gp42 in complex with mAb 10E4COMPLEXall0RECOMBINANT
2gH,gLCOMPLEX#1-#21RECOMBINANT
3100000COMPLEX#3-#41RECOMBINANT
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 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

SoftwareName: PHENIX / Version: 1.14_3259: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.54 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 402382 / Symmetry type: POINT

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