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Yorodumi- EMDB-33994: Cryo-EM structure of EBV gHgL-gp42 in complex with mAb 6H2 (local... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33994 | |||||||||
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Title | Cryo-EM structure of EBV gHgL-gp42 in complex with mAb 6H2 (localized refinement) | |||||||||
Map data | ||||||||||
Sample |
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Keywords | EBV / Cryo-EM / Glycoprotein / gHgL-gp42 complex / Antibody / VIRAL PROTEIN | |||||||||
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 | 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 | 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33994.map.gz | 323.9 MB | EMDB map data format | |
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Header (meta data) | emd-33994-v30.xml emd-33994.xml | 17.3 KB 17.3 KB | Display Display | EMDB header |
Images | emd_33994.png | 28.6 KB | ||
Filedesc metadata | emd-33994.cif.gz | 5.5 KB | ||
Others | emd_33994_half_map_1.map.gz emd_33994_half_map_2.map.gz | 318.7 MB 318.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33994 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33994 | HTTPS FTP |
-Validation report
Summary document | emd_33994_validation.pdf.gz | 993.2 KB | Display | EMDB validaton report |
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Full document | emd_33994_full_validation.pdf.gz | 992.7 KB | Display | |
Data in XML | emd_33994_validation.xml.gz | 17.2 KB | Display | |
Data in CIF | emd_33994_validation.cif.gz | 20.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33994 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33994 | HTTPS FTP |
-Related structure data
Related structure data | 7yp2MC 7yoyC 7yp1C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_33994.map.gz / Format: CCP4 / Size: 343 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.778 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_33994_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_33994_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : EBV gHgL-gp42 in complex with mAb 6H2
Entire | Name: EBV gHgL-gp42 in complex with mAb 6H2 |
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Components |
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-Supramolecule #1: EBV gHgL-gp42 in complex with mAb 6H2
Supramolecule | Name: EBV gHgL-gp42 in complex with mAb 6H2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: gH
Supramolecule | Name: gH / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Human gammaherpesvirus 4 (Epstein-Barr virus) |
-Supramolecule #3: 6H2
Supramolecule | Name: 6H2 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Macromolecule #1: Envelope glycoprotein H
Macromolecule | Name: Envelope glycoprotein H / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Human gammaherpesvirus 4 (Epstein-Barr virus) / Strain: GD1 |
Molecular weight | Theoretical: 34.79477 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MEELGHLTTE KQEYALRLAT VGYPKAGVYS GLIGGATSVL LSAYNRHPLF QPLHTVMRET LFIGSHVVLR ELRLNVTTQG PNLALYQLL STALCSALEI GEVLRGLALG TESGLFSPCY LSLRFDLTRD KLLSMAPQEA TLDQAAVSNA VDGFLGRLSL E REDRDAWH ...String: MEELGHLTTE KQEYALRLAT VGYPKAGVYS GLIGGATSVL LSAYNRHPLF QPLHTVMRET LFIGSHVVLR ELRLNVTTQG PNLALYQLL STALCSALEI GEVLRGLALG TESGLFSPCY LSLRFDLTRD KLLSMAPQEA TLDQAAVSNA VDGFLGRLSL E REDRDAWH LPAYKCVDRL DKVLMIIPLI NVTFIISSDR EVRGSALYEA STTYLSSSLF LSPVIMNKCS QGAVAGEPRQ IP KIQNFTR TQKSCIFCGF ALLSYDEKEG LETTTYITSQ EVQNSILSSN YFDFDNLHVH YLLLTTNGTV MEIAGLY UniProtKB: Envelope glycoprotein H |
-Macromolecule #2: 6H2 heavy chain
Macromolecule | Name: 6H2 heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 13.220722 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVKLLESGGG LVQPGGSLKL SCAASGFDFS RYWMTWVRQA PGQGLEWIGE INPDSSTINY TPSLKDKFII SRDNAKNTLY LQVSKLRSE DTALYYCARS PYYYGSSYDV WGAGTAVTVS S |
-Macromolecule #3: 6H2 light chain
Macromolecule | Name: 6H2 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 12.314811 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIVMSQSPSS LAVSAGEKVT MNCKSSQSLL NSRTRKNYLA WYQQKPGQSP KLLIYWASTR ESGVPDRFTG SGSGTDFTLT ISSVQAEDL AFYYCKQSYN LPTFGGGTKL EIK |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TECNAI F30 |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Tecnai F30 / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.52 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 402382 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |