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- PDB-8vbm: Structure of bovine anti-HIV Fab ElsE7 -

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Basic information

Entry
Database: PDB / ID: 8vbm
TitleStructure of bovine anti-HIV Fab ElsE7
Components
  • Bovine Fab ElsE7 heavy chain
  • Bovine Fab ElsE7 light chain
KeywordsIMMUNE SYSTEM / antibody / Fab fragment / bovine
Biological speciesBos taurus (cattle)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.54 Å
AuthorsStanfield, R.L. / Wilson, I.A.
Funding support United States, 1items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationINV-034657 United States
CitationJournal: 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
DepositionDec 12, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 4, 2024Provider: repository / Type: Initial release
Revision 1.1Sep 25, 2024Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
L: Bovine Fab ElsE7 light chain
H: Bovine Fab ElsE7 heavy chain


Theoretical massNumber of molelcules
Total (without water)50,3602
Polymers50,3602
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3800 Å2
ΔGint-23 kcal/mol
Surface area21830 Å2
MethodPISA
Unit cell
Length a, b, c (Å)58.215, 70.612, 123.974
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

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Components

#1: Antibody Bovine Fab ElsE7 light chain


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)
#2: Antibody Bovine Fab ElsE7 heavy chain


Mass: 27831.916 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Bos taurus (cattle) / Production host: Homo sapiens (human)
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 2.53 Å3/Da / Density % sol: 51.38 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 9.5 / Details: 0.1M CHES, pH 9.5, 20% Peg 8000

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 0.97946 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Nov 5, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97946 Å / Relative weight: 1
ReflectionResolution: 2.54→42.23 Å / Num. obs: 16971 / % possible obs: 96.8 % / Redundancy: 4.5 % / Biso Wilson estimate: 43.81 Å2 / CC1/2: 0.99 / Rmerge(I) obs: 0.164 / Rpim(I) all: 0.086 / Rrim(I) all: 0.186 / Net I/σ(I): 7.5
Reflection shellResolution: 2.54→2.63 Å / Redundancy: 4.2 % / Rmerge(I) obs: 1.35 / Mean I/σ(I) obs: 1.5 / Num. unique obs: 1511 / CC1/2: 0.4 / Rpim(I) all: 0.742 / Rrim(I) all: 1.55 / % possible all: 85.6

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Processing

Software
NameVersionClassification
PHENIX1.19.2_4158refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.54→42.23 Å / SU ML: 0.4684 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 33.9946
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2897 783 4.64 %
Rwork0.2346 16104 -
obs0.2371 16887 96.86 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 61.13 Å2
Refinement stepCycle: LAST / Resolution: 2.54→42.23 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3463 0 0 0 3463
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00183538
X-RAY DIFFRACTIONf_angle_d0.50624834
X-RAY DIFFRACTIONf_chiral_restr0.0415568
X-RAY DIFFRACTIONf_plane_restr0.0045621
X-RAY DIFFRACTIONf_dihedral_angle_d10.71161241
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.54-2.70.46761220.37812441X-RAY DIFFRACTION90.25
2.7-2.910.41651240.3332713X-RAY DIFFRACTION99.23
2.91-3.20.34791390.2952640X-RAY DIFFRACTION97.41
3.2-3.660.3221480.25572727X-RAY DIFFRACTION99.07
3.66-4.620.2371060.19692755X-RAY DIFFRACTION98.15
4.62-42.230.21721440.1752828X-RAY DIFFRACTION96.97

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