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Yorodumi- PDB-4od3: Crystal structure of human Fab CAP256-VRC26.07, a potent V1V2-dir... -
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-Basic information
Entry | Database: PDB / ID: 4od3 | ||||||
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Title | Crystal structure of human Fab CAP256-VRC26.07, a potent V1V2-directed HIV-1 neutralizing antibody | ||||||
Components |
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Keywords | IMMUNE SYSTEM / Fab / HIV-1 / V1V2 / CAP256 / VRC26 | ||||||
Function / homology | Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta Function and homology information | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.616 Å | ||||||
Authors | Gorman, J. / Doria-Rose, N.A. / Schramm, C.A. / Moore, P.L. / Mascola, J.R. / Shapiro, L. / Morris, L. / Kwong, P.D. | ||||||
Citation | Journal: Nature / Year: 2014 Title: Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Authors: Nicole A Doria-Rose / Chaim A Schramm / Jason Gorman / Penny L Moore / Jinal N Bhiman / Brandon J DeKosky / Michael J Ernandes / Ivelin S Georgiev / Helen J Kim / Marie Pancera / Ryan P ...Authors: Nicole A Doria-Rose / Chaim A Schramm / Jason Gorman / Penny L Moore / Jinal N Bhiman / Brandon J DeKosky / Michael J Ernandes / Ivelin S Georgiev / Helen J Kim / Marie Pancera / Ryan P Staupe / Han R Altae-Tran / Robert T Bailer / Ema T Crooks / Albert Cupo / Aliaksandr Druz / Nigel J Garrett / Kam H Hoi / Rui Kong / Mark K Louder / Nancy S Longo / Krisha McKee / Molati Nonyane / Sijy O'Dell / Ryan S Roark / Rebecca S Rudicell / Stephen D Schmidt / Daniel J Sheward / Cinque Soto / Constantinos Kurt Wibmer / Yongping Yang / Zhenhai Zhang / / James C Mullikin / James M Binley / Rogier W Sanders / Ian A Wilson / John P Moore / Andrew B Ward / George Georgiou / Carolyn Williamson / Salim S Abdool Karim / Lynn Morris / Peter D Kwong / Lawrence Shapiro / John R Mascola / Abstract: Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental ...Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30-38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4od3.cif.gz | 255 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4od3.ent.gz | 209.9 KB | Display | PDB format |
PDBx/mmJSON format | 4od3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4od3_validation.pdf.gz | 448 KB | Display | wwPDB validaton report |
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Full document | 4od3_full_validation.pdf.gz | 449.4 KB | Display | |
Data in XML | 4od3_validation.xml.gz | 17.4 KB | Display | |
Data in CIF | 4od3_validation.cif.gz | 23.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/od/4od3 ftp://data.pdbj.org/pub/pdb/validation_reports/od/4od3 | HTTPS FTP |
-Related structure data
Related structure data | 5856C 4ocrC 4ocsC 4ocwC 4od1C 4odhC 4orgC 3u2sS C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data |
-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: 22989.518 Da / Num. of mol.: 1 / Fragment: Fab Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Plasmid: pVRC8400 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) | ||||||
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#2: Antibody | Mass: 28119.502 Da / Num. of mol.: 1 / Fragment: Fab Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Plasmid: pVRC8400 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) | ||||||
#3: Chemical | #4: Chemical | ChemComp-MES / | #5: Water | ChemComp-HOH / | Has protein modification | Y | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.38 Å3/Da / Density % sol: 63.59 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6 Details: 4% PEG8000, 0.1 M zinc acetate, 0.1 M MES, pH 6, cryoprotectant: 20% glycerol, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Apr 4, 2013 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: double crystal Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.616→50 Å / Num. all: 19943 / Num. obs: 19943 / % possible obs: 93.9 % / Observed criterion σ(F): -3 / Observed criterion σ(I): -3 / Rmerge(I) obs: 0.13 / Net I/σ(I): 12.5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 3U2S Resolution: 2.616→39.904 Å / SU ML: 0.29 / σ(F): 1.35 / Phase error: 30.29 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.616→39.904 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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