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- PDB-7u0k: IOMA class antibody Fab ACS124 -

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Basic information

Entry
Database: PDB / ID: 7u0k
TitleIOMA class antibody Fab ACS124
Components
  • IOMA Class antibody ACS124 Heavy chain
  • IOMA Class antibody ACS124 Light chain
KeywordsIMMUNE SYSTEM / HIV
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.73 Å
AuthorsFarokhi, E. / Stanfield, R.L. / Wilson, I.A.
Funding support United States, 1items
OrganizationGrant numberCountry
Consortia for HIV/AIDS Vaccine Development United States
CitationJournal: Nat Commun / Year: 2022
Title: Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein.
Authors: Jelle van Schooten / Elinaz Farokhi / Anna Schorcht / Tom L G M van den Kerkhof / Hongmei Gao / Patricia van der Woude / Judith A Burger / Tim G Rijkhold Meesters / Tom Bijl / Riham ...Authors: Jelle van Schooten / Elinaz Farokhi / Anna Schorcht / Tom L G M van den Kerkhof / Hongmei Gao / Patricia van der Woude / Judith A Burger / Tim G Rijkhold Meesters / Tom Bijl / Riham Ghalaiyini / Hannah L Turner / Jessica Dorning / Barbera D C van Schaik / Antoine H C van Kampen / Celia C Labranche / Robyn L Stanfield / Devin Sok / David C Montefiori / Dennis R Burton / Michael S Seaman / Gabriel Ozorowski / Ian A Wilson / Rogier W Sanders / Andrew B Ward / Marit J van Gils /
Abstract: A major goal of current HIV-1 vaccine design efforts is to induce broadly neutralizing antibodies (bNAbs). The VH1-2-derived bNAb IOMA directed to the CD4-binding site of the HIV-1 envelope ...A major goal of current HIV-1 vaccine design efforts is to induce broadly neutralizing antibodies (bNAbs). The VH1-2-derived bNAb IOMA directed to the CD4-binding site of the HIV-1 envelope glycoprotein is of interest because, unlike the better-known VH1-2-derived VRC01-class bNAbs, it does not require a rare short light chain complementarity-determining region 3 (CDRL3). Here, we describe three IOMA-class NAbs, ACS101-103, with up to 37% breadth, that share many characteristics with IOMA, including an average-length CDRL3. Cryo-electron microscopy revealed that ACS101 shares interactions with those observed with other VH1-2 and VH1-46-class bNAbs, but exhibits a unique binding mode to residues in loop D. Analysis of longitudinal sequences from the patient suggests that a transmitter/founder-virus lacking the N276 glycan might have initiated the development of these NAbs. Together these data strengthen the rationale for germline-targeting vaccination strategies to induce IOMA-class bNAbs and provide a wealth of sequence and structural information to support such strategies.
History
DepositionFeb 18, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 24, 2022Provider: repository / Type: Initial release
Revision 1.1Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
L: IOMA Class antibody ACS124 Light chain
H: IOMA Class antibody ACS124 Heavy chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)47,9654
Polymers47,5502
Non-polymers4152
Water4,017223
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration, This is a Fab a heterodimer of one heavy chain and one light chain
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4650 Å2
ΔGint-21 kcal/mol
Surface area19270 Å2
MethodPISA
Unit cell
Length a, b, c (Å)62.452, 66.703, 101.939
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 IOMA Class antibody ACS124 Light chain


Mass: 22946.445 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human)
#2: Antibody IOMA Class antibody ACS124 Heavy chain


Mass: 24603.680 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human)
#3: Chemical ChemComp-NHE / 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID / N-CYCLOHEXYLTAURINE / CHES / CHES (buffer)


Mass: 207.290 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C8H17NO3S / Comment: pH buffer*YM
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 223 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN

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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: 2.23 Å3/Da / Density % sol: 44.91 %
Crystal growTemperature: 293.15 K / Method: vapor diffusion, sitting drop
Details: 0.1M of CHES (pH 9.5) and 38% (v/v) polyethylene glycol 600

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-1 / Wavelength: 0.97946 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: May 21, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97946 Å / Relative weight: 1
ReflectionResolution: 1.73→33.98 Å / Num. obs: 46469 / % possible obs: 98.9 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 12 % / Biso Wilson estimate: 27.03 Å2 / CC1/2: 0.89 / Rmerge(I) obs: 0.155 / Rpim(I) all: 0.046 / Rrim(I) all: 0.162 / Net I/σ(I): 36.3
Reflection shellResolution: 1.73→1.74 Å / Redundancy: 11.9 % / Rmerge(I) obs: 1.79 / Mean I/σ(I) obs: 1.3 / Num. unique obs: 2300 / CC1/2: 0.47 / Rpim(I) all: 0.526 / Rrim(I) all: 1.87 / % possible all: 99.7

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Processing

Software
NameVersionClassification
PHENIX1.19.2_4158refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5F7E

5f7e


Resolution: 1.73→33.98 Å / SU ML: 0.2307 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 24.1959
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2225 2018 4.54 %
Rwork0.1855 42422 -
obs0.1872 44440 98.35 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 36.77 Å2
Refinement stepCycle: LAST / Resolution: 1.73→33.98 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3300 0 26 223 3549
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01073410
X-RAY DIFFRACTIONf_angle_d1.14914658
X-RAY DIFFRACTIONf_chiral_restr0.2143529
X-RAY DIFFRACTIONf_plane_restr0.0081591
X-RAY DIFFRACTIONf_dihedral_angle_d14.37421223
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.73-1.770.39171560.31092781X-RAY DIFFRACTION92.62
1.77-1.820.28651210.26173058X-RAY DIFFRACTION99.84
1.82-1.870.28661460.23333046X-RAY DIFFRACTION99.91
1.87-1.940.2651480.2243009X-RAY DIFFRACTION99.59
1.94-20.26541390.2263037X-RAY DIFFRACTION99.72
2-2.080.23081450.21393023X-RAY DIFFRACTION98.69
2.08-2.180.30021350.19762905X-RAY DIFFRACTION94.79
2.18-2.290.24031440.18823043X-RAY DIFFRACTION99.78
2.29-2.440.20781510.18983049X-RAY DIFFRACTION99.32
2.44-2.630.22561440.1923044X-RAY DIFFRACTION99.25
2.63-2.890.271450.19393073X-RAY DIFFRACTION99.08
2.89-3.310.22181430.18672982X-RAY DIFFRACTION96.15
3.31-4.170.19441440.16523151X-RAY DIFFRACTION99.7
4.17-33.980.18211570.16063221X-RAY DIFFRACTION98.37

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