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Yorodumi- PDB-6c5v: An anti-gH/gL antibody that neutralizes dual-tropic infection def... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6c5v | ||||||||||||
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Title | An anti-gH/gL antibody that neutralizes dual-tropic infection defines a site of vulnerability on Epstein-Barr virus | ||||||||||||
Components |
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Keywords | VIRAL PROTEIN / Epstein-Barr virus / neutralizing antibodies / gH/gL / glycoproteins / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID | ||||||||||||
Function / homology | Function and homology information host cell endosome membrane / carbohydrate binding / host cell Golgi apparatus / membrane => GO:0016020 / fusion of virus membrane with host plasma membrane / viral envelope / host cell plasma membrane / virion membrane / membrane Similarity search - Function | ||||||||||||
Biological species | Human herpesvirus 4 (Epstein-Barr virus) Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.8 Å | ||||||||||||
Authors | Snijder, J. / Ortego, M.S. / Weidle, C. / Stuart, A.B. / Gray, M.A. / McElrath, M.J. / Pancera, M. / Veesler, D. / McGuire, A.T. / Seattle Structural Genomics Center for Infectious Disease (SSGCID) | ||||||||||||
Funding support | United States, 2items
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Citation | Journal: Immunity / Year: 2018 Title: An Antibody Targeting the Fusion Machinery Neutralizes Dual-Tropic Infection and Defines a Site of Vulnerability on Epstein-Barr Virus. Authors: Joost Snijder / Michael S Ortego / Connor Weidle / Andrew B Stuart / Matthew D Gray / M Juliana McElrath / Marie Pancera / David Veesler / Andrew T McGuire / Abstract: Epstein-Barr virus (EBV) is a causative agent of infectious mononucleosis and is associated with 200,000 new cases of cancer and 140,000 deaths annually. Subunit vaccines against this pathogen have ...Epstein-Barr virus (EBV) is a causative agent of infectious mononucleosis and is associated with 200,000 new cases of cancer and 140,000 deaths annually. Subunit vaccines against this pathogen have focused on the gp350 glycoprotein and remain unsuccessful. We isolated human antibodies recognizing the EBV fusion machinery (gH/gL and gB) from rare memory B cells. One anti-gH/gL antibody, AMMO1, potently neutralized infection of B cells and epithelial cells, the two major cell types targeted by EBV. We determined a cryo-electron microscopy reconstruction of the gH/gL-gp42-AMMO1 complex and demonstrated that AMMO1 bound to a discontinuous epitope formed by both gH and gL at the Domain-I/Domain-II interface. Integrating structural, biochemical, and infectivity data, we propose that AMMO1 inhibits fusion of the viral and cellular membranes. This work identifies a crucial epitope that may aid in the design of next-generation subunit vaccines against this major public health burden. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6c5v.cif.gz | 274 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6c5v.ent.gz | 218.6 KB | Display | PDB format |
PDBx/mmJSON format | 6c5v.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6c5v_validation.pdf.gz | 826.2 KB | Display | wwPDB validaton report |
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Full document | 6c5v_full_validation.pdf.gz | 829.1 KB | Display | |
Data in XML | 6c5v_validation.xml.gz | 40.5 KB | Display | |
Data in CIF | 6c5v_validation.cif.gz | 61.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c5/6c5v ftp://data.pdbj.org/pub/pdb/validation_reports/c5/6c5v | HTTPS FTP |
-Related structure data
Related structure data | 7344MC 7345C 6blaC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Envelope glycoprotein ... , 2 types, 2 molecules AB
#1: Protein | Mass: 77091.547 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human herpesvirus 4 (Epstein-Barr virus) Strain: GD1 / Gene: BXLF2, gH / Cell line (production host): 293 / Production host: Homo sapiens (human) / References: UniProt: K9US75 |
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#2: Protein | Mass: 15145.395 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human herpesvirus 4 (Epstein-Barr virus) Strain: AG876 / Gene: gL, BKRF2 / Cell line (production host): 293 / Production host: Homo sapiens (human) / References: UniProt: Q1HVF6 |
-Protein , 1 types, 1 molecules C
#3: Protein | Mass: 25356.859 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human herpesvirus 4 (Epstein-Barr virus) Strain: GD1 / Gene: BZLF2 / Cell (production host): 293 / Production host: Homo sapiens (human) / References: UniProt: P0C6Z5 |
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-Antibody , 2 types, 2 molecules HL
#4: Antibody | Mass: 23982.885 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell (production host): 293 / Production host: Homo sapiens (human) |
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#5: Antibody | Mass: 23095.514 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): 293 / Production host: Homo sapiens (human) |
-Sugars , 2 types, 9 molecules
#6: Polysaccharide | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
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#7: Sugar | ChemComp-NAG / |
-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 |
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-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: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 65 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 4.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 72000 / Symmetry type: POINT |