+Open data
-Basic information
Entry | Database: PDB / ID: 8vbj | ||||||
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Title | Structure of bovine anti-HIV Fab ElsE2 | ||||||
Components |
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Keywords | IMMUNE SYSTEM / antibody / Fab fragment / bovine | ||||||
Function / homology | : Function and homology information | ||||||
Biological species | Bos taurus (cattle) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å | ||||||
Authors | Stanfield, R.L. / Wilson, I.A. | ||||||
Funding support | United States, 1items
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Citation | Journal: PLoS Pathog / Year: 2024 Title: Immunization of cows with HIV envelope trimers generates broadly neutralizing antibodies to the V2-apex from the ultralong CDRH3 repertoire. Authors: Pilar X Altman / Gabriel Ozorowski / Robyn L Stanfield / Jeremy Haakenson / Michael Appel / Mara Parren / Wen-Hsin Lee / Huldah Sang / Jordan Woehl / Karen Saye-Francisco / Leigh M Sewall / ...Authors: Pilar X Altman / Gabriel Ozorowski / Robyn L Stanfield / Jeremy Haakenson / Michael Appel / Mara Parren / Wen-Hsin Lee / Huldah Sang / Jordan Woehl / Karen Saye-Francisco / Leigh M Sewall / Collin Joyce / Ge Song / Katelyn Porter / Elise Landais / Raiees Andrabi / Ian A Wilson / Andrew B Ward / Waithaka Mwangi / Vaughn V Smider / Dennis R Burton / Devin Sok / Abstract: The generation of broadly neutralizing antibodies (bnAbs) to conserved epitopes on HIV Envelope (Env) is one of the cornerstones of HIV vaccine research. The animal models commonly used for HIV do ...The generation of broadly neutralizing antibodies (bnAbs) to conserved epitopes on HIV Envelope (Env) is one of the cornerstones of HIV vaccine research. The animal models commonly used for HIV do not reliably produce a potent broadly neutralizing serum antibody response, with the exception of cows. Cows have previously produced a CD4 binding site response by homologous prime and boosting with a native-like Env trimer. In small animal models, other engineered immunogens were shown to focus antibody responses to the bnAb V2-apex region of Env. Here, we immunized two groups of cows (n = 4) with two regimens of V2-apex focusing Env immunogens to investigate whether antibody responses could be generated to the V2-apex on Env. Group 1 was immunized with chimpanzee simian immunodeficiency virus (SIV)-Env trimer that shares its V2-apex with HIV, followed by immunization with C108, a V2-apex focusing immunogen, and finally boosted with a cross-clade native-like trimer cocktail. Group 2 was immunized with HIV C108 Env trimer followed by the same HIV trimer cocktail as Group 1. Longitudinal serum analysis showed that one cow in each group developed serum neutralizing antibody responses to the V2-apex. Eight and 11 bnAbs were isolated from Group 1 and Group 2 cows, respectively, and showed moderate breadth and potency. Potent and broad responses in this study developed much later than previous cow immunizations that elicited CD4bs bnAbs responses and required several different immunogens. All isolated bnAbs were derived from the ultralong CDRH3 repertoire. The finding that cow antibodies can target more than one broadly neutralizing epitope on the HIV surface reveals the generality of elongated structures for the recognition of highly glycosylated proteins. The exclusive isolation of ultralong CDRH3 bnAbs, despite only comprising a small percent of the cow repertoire, suggests these antibodies outcompete the long and short CDRH3 antibodies during the bnAb response. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8vbj.cif.gz | 200.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8vbj.ent.gz | 147 KB | Display | PDB format |
PDBx/mmJSON format | 8vbj.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8vbj_validation.pdf.gz | 438.8 KB | Display | wwPDB validaton report |
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Full document | 8vbj_full_validation.pdf.gz | 440.7 KB | Display | |
Data in XML | 8vbj_validation.xml.gz | 25 KB | Display | |
Data in CIF | 8vbj_validation.cif.gz | 34.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vb/8vbj ftp://data.pdbj.org/pub/pdb/validation_reports/vb/8vbj | HTTPS FTP |
-Related structure data
Related structure data | 8tq1C 8vbkC 8vblC 8vbmC 8vbnC 8vboC 8vbpC 8vbqC 8vbrC 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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Unit cell |
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Components on special symmetry positions |
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-Components
#1: Antibody | Mass: 22527.611 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Cell line (production host): expi293F / Organ (production host): Kidney / Production host: Homo sapiens (human) |
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#2: Antibody | Mass: 28086.158 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Cell line (production host): expi293F / Organ (production host): Kidney / Production host: Homo sapiens (human) |
#3: Chemical | ChemComp-K / |
#4: Chemical | ChemComp-SO4 / |
#5: Water | ChemComp-HOH / |
Has ligand of interest | N |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.29 Å3/Da / Density % sol: 62.6 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: 0.1M Tris, pH 8.5, 1.5M ammonium sulfate, 12% glycerol |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.97946 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Nov 5, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97946 Å / Relative weight: 1 |
Reflection | Resolution: 1.9→45.48 Å / Num. obs: 51953 / % possible obs: 98.8 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 8.5 % / Biso Wilson estimate: 23.31 Å2 / CC1/2: 0.995 / Rmerge(I) obs: 0.224 / Rpim(I) all: 0.079 / Rrim(I) all: 0.238 / Net I/σ(I): 8.4 |
Reflection shell | Resolution: 1.9→1.97 Å / Redundancy: 8.7 % / Rmerge(I) obs: 2.24 / Mean I/σ(I) obs: 1.4 / Num. unique obs: 5160 / CC1/2: 0.413 / Rpim(I) all: 0.776 / Rrim(I) all: 2.38 / % possible all: 99.2 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.9→45.48 Å / SU ML: 0.2665 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 25.0404 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 30.7 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.9→45.48 Å
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Refine LS restraints |
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LS refinement shell |
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