+Open data
-Basic information
Entry | Database: PDB / ID: 7ui0 | ||||||
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Title | Post-fusion ectodomain of HSV-1 gB in complex with HSV010-13 Fab | ||||||
Components |
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Keywords | VIRAL PROTEIN/Immune System / glycoprotein / fusogen / antibody / ADCC / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex | ||||||
Function / homology | Function and homology information host cell Golgi membrane / host cell endosome membrane / symbiont entry into host cell / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / identical protein binding / membrane Similarity search - Function | ||||||
Biological species | Human alphaherpesvirus 1 strain KOS Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||
Authors | Windsor, I.W. / Kong, S.L. / Garforth, S.J. / Almo, S.C. / Harrison, S.C. | ||||||
Funding support | United States, 1items
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Citation | Journal: J Clin Invest / Year: 2023 Title: A non-neutralizing glycoprotein B monoclonal antibody protects against herpes simplex virus disease in mice. Authors: Masayuki Kuraoka / Clare Burn Aschner / Ian W Windsor / Aakash Mahant Mahant / Scott J Garforth / Susan Luozheng Kong / Jacqueline M Achkar / Steven C Almo / Garnett Kelsoe / Betsy C Herold / Abstract: There is an unmet need for monoclonal antibodies (mAbs) for prevention or as adjunctive treatment of herpes simplex virus (HSV) disease. Most vaccine and mAb efforts focus on neutralizing antibodies, ...There is an unmet need for monoclonal antibodies (mAbs) for prevention or as adjunctive treatment of herpes simplex virus (HSV) disease. Most vaccine and mAb efforts focus on neutralizing antibodies, but for HSV this strategy has proven ineffective. Preclinical studies with a candidate HSV vaccine strain, ΔgD-2, demonstrated that non-neutralizing antibodies that activate Fcγ receptors (FcγRs) to mediate antibody-dependent cellular cytotoxicity (ADCC) provide active and passive protection against HSV-1 and HSV-2. We hypothesized that this vaccine provides a tool to identify and characterize protective mAbs. We isolated HSV-specific mAbs from germinal center and memory B cells and bone marrow plasmacytes of ΔgD-2-vaccinated mice and evaluated these mAbs for binding, neutralizing, and FcγR-activating activity and for protective efficacy in mice. The most potent protective mAb, BMPC-23, was not neutralizing but activated murine FcγRIV, a biomarker of ADCC. The cryo-electron microscopic structure of the Fab-glycoprotein B (gB) assembly identified domain IV of gB as the epitope. A single dose of BMPC-23 administered 24 hours before or after viral challenge provided significant protection when configured as mouse IgG2c and protected mice expressing human FcγRIII when engineered as a human IgG1. These results highlight the importance of FcR-activating antibodies in protecting against HSV. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7ui0.cif.gz | 417.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7ui0.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 7ui0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7ui0_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7ui0_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 7ui0_validation.xml.gz | 73.9 KB | Display | |
Data in CIF | 7ui0_validation.cif.gz | 111.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ui/7ui0 ftp://data.pdbj.org/pub/pdb/validation_reports/ui/7ui0 | HTTPS FTP |
-Related structure data
Related structure data | 26521MC 7uhzC 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: 71668.188 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human alphaherpesvirus 1 strain KOS / Strain: KOS / Gene: gB, UL27 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P06437 #2: Antibody | Mass: 13043.623 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human) #3: Antibody | Mass: 11886.177 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human) |
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-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: Trimeric, post-fusion HSV-1 gB in complex with three HSV010-13 Fabs Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Mus musculus (house mouse) |
Source (recombinant) | Organism: Homo sapiens (human) |
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 / Nominal defocus max: 1800 nm / Nominal defocus min: 600 nm |
Image recording | Electron dose: 55.3 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 123068 / Symmetry type: POINT |