+Open data
-Basic information
Entry | Database: PDB / ID: 8khr | ||||||
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Title | Cryo-EM structure of EBV gH/gL-gp42 in complex with fab 2C1 | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Human gammaherpesvirus 4 / Neutralizing antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | Function and homology information host cell membrane / host cell endosome / carbohydrate binding / host cell Golgi apparatus / 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 | Epstein-Barr virus (Epstein-Barr virus) Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.25 Å | ||||||
Authors | Fang, X.Y. / Zhao, G.X. / Zeng, M.S. / Liu, Z. | ||||||
Funding support | China, 1items
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Citation | Journal: Cell Rep Med / Year: 2024 Title: Potent human monoclonal antibodies targeting Epstein-Barr virus gp42 reveal vulnerable sites for virus infection. Authors: Ge-Xin Zhao / Xin-Yan Fang / Guo-Long Bu / Shuai-Jia-Bin Chen / Cong Sun / Ting Li / Chu Xie / Yu Wang / Shu-Xin Li / Ning Meng / Guo-Kai Feng / Qian Zhong / Xiang-Wei Kong / Zheng Liu / Mu-Sheng Zeng / Abstract: Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its ...Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8khr.cif.gz | 256.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8khr.ent.gz | 191.5 KB | Display | PDB format |
PDBx/mmJSON format | 8khr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8khr_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 8khr_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8khr_validation.xml.gz | 49.1 KB | Display | |
Data in CIF | 8khr_validation.cif.gz | 72.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kh/8khr ftp://data.pdbj.org/pub/pdb/validation_reports/kh/8khr | HTTPS FTP |
-Related structure data
Related structure data | 37249MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 22398.324 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Epstein-Barr virus (strain GD1) (Epstein-Barr virus) Gene: BZLF2 / Production host: Homo sapiens (human) / References: UniProt: P0C6Z5 |
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#2: Antibody | Mass: 11978.212 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
#3: Antibody | Mass: 11849.269 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
#4: Protein | Mass: 72600.352 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Epstein-Barr virus (strain GD1) (Epstein-Barr virus) Gene: BXLF2, gH / Production host: Homo sapiens (human) / References: UniProt: A0A0C7TVV8 |
#5: Protein | Mass: 11759.323 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Epstein-Barr virus (strain GD1) (Epstein-Barr virus) Gene: BKRF2, gL / Production host: Homo sapiens (human) / References: UniProt: A0A0C7TRA4 |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Pentamer complex of gH/gL-gp42 with fab 2C1 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Epstein-Barr virus (strain GD1) (Epstein-Barr virus) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 278 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.25 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 227428 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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