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- EMDB-33102: Cryo-EM structure of EBV glycoprotein complex gHgL-gp42 bound by ... -

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Entry
Database: EMDB / ID: EMD-33102
TitleCryo-EM structure of EBV glycoprotein complex gHgL-gp42 bound by a neutralizing antibody 6H2
Map data
Sample
  • Complex: Cryo-EM structure of EBV glycoprotein complex gHgL-gp42 bound by a neutralizing antibody 6H2
    • Complex: Cryo-EM structure of EBV glycoprotein complex gHgL-gp42 bound by a neutralizing antibody 6H2
    • Complex: nAbs 6H2
KeywordsEBV / Glycoprotein / Neutralizing antibody / Cryo-EM / VIRAL PROTEIN
Biological speciesHuman gammaherpesvirus 4 (Epstein-Barr virus) / Oryctolagus cuniculus (rabbit)
Methodsingle particle reconstruction / cryo EM / Resolution: 6.87 Å
AuthorsZheng Q / Hong J / Zhang X / Chen Y / Li S / Xia N
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: J Virol / Year: 2022
Title: A Neutralizing Antibody Targeting gH Provides Potent Protection against EBV Challenge .
Authors: Junping Hong / Ling Zhong / Qingbing Zheng / Qian Wu / Zhenghui Zha / Dongmei Wei / Haiwen Chen / Wanlin Zhang / Shanshan Zhang / Yang Huang / Kaiyun Chen / Junyu Chen / Shaowei Li / Mu- ...Authors: Junping Hong / Ling Zhong / Qingbing Zheng / Qian Wu / Zhenghui Zha / Dongmei Wei / Haiwen Chen / Wanlin Zhang / Shanshan Zhang / Yang Huang / Kaiyun Chen / Junyu Chen / Shaowei Li / Mu-Sheng Zeng / Yi-Xin Zeng / Ningshao Xia / Xiao Zhang / Miao Xu / Yixin Chen /
Abstract: Epstein-Barr virus (EBV) is an oncogenic herpesvirus that is associated with 200,000 new cases of cancer and 140,000 deaths annually. To date, there are no available vaccines or therapeutics for ...Epstein-Barr virus (EBV) is an oncogenic herpesvirus that is associated with 200,000 new cases of cancer and 140,000 deaths annually. To date, there are no available vaccines or therapeutics for clinical usage. Recently, the viral heterodimer glycoprotein gH/gL has become a promising target for the development of prophylactic vaccines against EBV. Here, we developed the anti-gH antibody 6H2 and its chimeric version C6H2, which had full neutralizing activity in epithelial cells and partial neutralizing activity in B cells. C6H2 exhibited potent protection against lethal EBV challenge in a humanized mouse model. The cryo-electron microscopy (cryo-EM) structure further revealed that 6H2 recognized a previously unidentified epitope on gH/gL D-IV that is critical for viral attachment and subsequent membrane fusion with epithelial cells. Our results suggest that C6H2 is a promising candidate in the prevention of EBV-induced lymphoproliferative diseases (LPDs) and may inform the design of an EBV vaccine. Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that establishes lifelong persistence and is related to multiple diseases, including cancers. Neutralizing antibodies (NAbs) have proven to be highly effective in preventing EBV infection and subsequent diseases. Here, we developed an anti-EBV-gH NAb, 6H2, which blocked EBV infection and . This 6H2 neutralizing epitope should be helpful to understand EBV infection mechanisms and guide the development of vaccines and therapeutics against EBV infection.
History
DepositionMar 21, 2022-
Header (metadata) releaseSep 21, 2022-
Map releaseSep 21, 2022-
UpdateSep 13, 2023-
Current statusSep 13, 2023Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_33102.png

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Map

FileDownload / File: emd_33102.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.1 Å
Density
Contour LevelBy AUTHOR: 0.3
Minimum - Maximum-0.45060644 - 0.96318644
Average (Standard dev.)0.003918027 (±0.047806986)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions240240240
Spacing240240240
CellA=B=C: 264.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_33102_half_map_1.map
Projections & Slices
AxesZYX

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Half map: #2

Fileemd_33102_half_map_2.map
Projections & Slices
AxesZYX

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Sample components

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Entire : Cryo-EM structure of EBV glycoprotein complex gHgL-gp42 bound by ...

EntireName: Cryo-EM structure of EBV glycoprotein complex gHgL-gp42 bound by a neutralizing antibody 6H2
Components
  • Complex: Cryo-EM structure of EBV glycoprotein complex gHgL-gp42 bound by a neutralizing antibody 6H2
    • Complex: Cryo-EM structure of EBV glycoprotein complex gHgL-gp42 bound by a neutralizing antibody 6H2
    • Complex: nAbs 6H2

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Supramolecule #1: Cryo-EM structure of EBV glycoprotein complex gHgL-gp42 bound by ...

SupramoleculeName: Cryo-EM structure of EBV glycoprotein complex gHgL-gp42 bound by a neutralizing antibody 6H2
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#7

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Supramolecule #2: Cryo-EM structure of EBV glycoprotein complex gHgL-gp42 bound by ...

SupramoleculeName: Cryo-EM structure of EBV glycoprotein complex gHgL-gp42 bound by a neutralizing antibody 6H2
type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Human gammaherpesvirus 4 (Epstein-Barr virus)

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Supramolecule #3: nAbs 6H2

SupramoleculeName: nAbs 6H2 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#7
Source (natural)Organism: Oryctolagus cuniculus (rabbit)

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.2 µm
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 60.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 6.87 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 58582

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