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- PDB-8uki: Crystal structure of 04_A06 Fab -

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Basic information

Entry
Database: PDB / ID: 8uki
TitleCrystal structure of 04_A06 Fab
Components
  • 04_A06 Fab Heavy Chain
  • 04_A06 Fab Light Chain
KeywordsIMMUNE SYSTEM / Fab / broadly neutralizing antibody / HIV-1 / CD4 binding site
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.75 Å
AuthorsDeLaitsch, A.T. / Gristick, H.B. / Bjorkman, P.J.
Funding support United States, 1items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationINV-002143 United States
CitationJournal: Nat Immunol / Year: 2025
Title: Profiling of HIV-1 elite neutralizer cohort reveals a CD4bs bnAb for HIV-1 prevention and therapy.
Authors: Lutz Gieselmann / Andrew T DeLaitsch / Malena Rohde / Henning Gruell / Christoph Kreer / Meryem Seda Ercanoglu / Harry B Gristick / Philipp Schommers / Elvin Ahmadov / Caelan Radford / ...Authors: Lutz Gieselmann / Andrew T DeLaitsch / Malena Rohde / Henning Gruell / Christoph Kreer / Meryem Seda Ercanoglu / Harry B Gristick / Philipp Schommers / Elvin Ahmadov / Caelan Radford / Andrea Mazzolini / Lily Zhang / Anthony P West / Johanna Worczinski / Anna Momot / Maren L Reichwein / Jacqueline Knüfer / Ricarda Stumpf / Nonhlanhla N Mkhize / Haajira Kaldine / Sinethemba Bhebhe / Sharvari Deshpande / Federico Giovannoni / Erin Stefanutti / Fabio Benigni / Colin Havenar-Daughton / Davide Corti / Arne Kroidl / Anurag Adhikari / Aubin J Nanfack / Georgia E Ambada / Ralf Duerr / Lucas Maganga / Wiston William / Nyanda E Ntinginya / Timo Wolf / Christof Geldmacher / Michael Hoelscher / Clara Lehmann / Penny L Moore / Thierry Mora / Aleksandra M Walczak / Peter B Gilbert / Nicole A Doria-Rose / Yunda Huang / Jesse D Bloom / Michael S Seaman / Pamela J Bjorkman / Florian Klein /
Abstract: Administration of HIV-1 neutralizing antibodies can suppress viremia and prevent infection in vivo. However, clinical use is challenged by envelope diversity and rapid viral escape. Here, we ...Administration of HIV-1 neutralizing antibodies can suppress viremia and prevent infection in vivo. However, clinical use is challenged by envelope diversity and rapid viral escape. Here, we performed single B cell profiling of 32 top HIV-1 elite neutralizers to identify broadly neutralizing antibodies with highest antiviral activity. From 831 expressed monoclonal antibodies, we identified 04_A06, a V1-2-encoded broadly neutralizing antibody to the CD4 binding site with remarkable breadth and potency against multiclade pseudovirus panels (geometric mean half-maximal inhibitory concentration = 0.059 µg ml, breadth = 98.5%, 332 strains). Moreover, 04_A06 was not susceptible to classic CD4 binding site escape variants and maintained full viral suppression in HIV-1-infected humanized mice. Structural analyses revealed an unusually long 11-amino-acid heavy chain insertion that facilitates interprotomer contacts with highly conserved residues on the adjacent gp120 protomer. Finally, 04_A06 demonstrated high activity against contemporaneously circulating viruses from the Antibody-Mediated Prevention trials (geometric mean half-maximal inhibitory concentration = 0.082 µg ml, breadth = 98.4%, 191 virus strains), and in silico modeling for 04_A06LS predicted prevention efficacy of >93%. Thus, 04_A06 will provide unique opportunities for effective treatment and prevention of HIV-1 infection.
History
DepositionOct 13, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 16, 2025Provider: repository / Type: Initial release
Revision 1.1Oct 29, 2025Group: 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.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
H: 04_A06 Fab Heavy Chain
L: 04_A06 Fab Light Chain


Theoretical massNumber of molelcules
Total (without water)49,8342
Polymers49,8342
Non-polymers00
Water8,215456
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3260 Å2
ΔGint-20 kcal/mol
Surface area19170 Å2
MethodPISA
Unit cell
Length a, b, c (Å)42.680, 133.280, 43.360
Angle α, β, γ (deg.)90.00, 111.26, 90.00
Int Tables number4
Space group name H-MP1211

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Components

#1: Antibody 04_A06 Fab Heavy Chain


Mass: 26690.879 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell (production host): HEK293 / Production host: Homo sapiens (human)
#2: Antibody 04_A06 Fab Light Chain


Mass: 23142.639 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell (production host): HEK293 / Production host: Homo sapiens (human)
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 456 / Source method: isolated from a natural source / Formula: H2O
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: 2.31 Å3/Da / Density % sol: 46.67 %
Crystal growTemperature: 295 K / Method: vapor diffusion, sitting drop / Details: 8% v/v Tacsimate, pH 7.0, 20% w/v PEG3350

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Nov 3, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.65→38.7 Å / Num. obs: 52273 / % possible obs: 97 % / Redundancy: 6.6 % / CC1/2: 0.99 / Rmerge(I) obs: 0.12 / Rpim(I) all: 0.08 / Net I/σ(I): 7.7
Reflection shellResolution: 1.65→1.68 Å / Redundancy: 6.1 % / Rmerge(I) obs: 0.71 / Mean I/σ(I) obs: 1.8 / Num. unique obs: 2575 / CC1/2: 0.82 / Rpim(I) all: 0.45 / % possible all: 96

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Processing

Software
NameVersionClassification
PHENIXv1.20.1-4487refinement
iMOSFLMv7.4data reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 3NGB

3ngb


Resolution: 1.75→38.7 Å / Cross valid method: FREE R-VALUE
RfactorNum. reflection% reflection
Rfree0.205 --
Rwork0.17 --
obs-43827 96 %
Refinement stepCycle: LAST / Resolution: 1.75→38.7 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3239 0 0 456 3695

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