+Open data
-Basic information
Entry | Database: PDB / ID: 5ukn | |||||||||||||||
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Title | Structure of unliganded anti-gp120 CD4bs antibody DH522UCA Fab | |||||||||||||||
Components |
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Keywords | IMMUNE SYSTEM / HIV gp120 | |||||||||||||||
Function / homology | Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta Function and homology information | |||||||||||||||
Biological species | Macaca mulatta (Rhesus monkey) | |||||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.75 Å | |||||||||||||||
Authors | Nicely, N.I. | |||||||||||||||
Funding support | United States, 4items
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Citation | Journal: Nat Commun / Year: 2017 Title: Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations. Authors: Wilton B Williams / Jinsong Zhang / Chuancang Jiang / Nathan I Nicely / Daniela Fera / Kan Luo / M Anthony Moody / Hua-Xin Liao / S Munir Alam / Thomas B Kepler / Akshaya Ramesh / Kevin ...Authors: Wilton B Williams / Jinsong Zhang / Chuancang Jiang / Nathan I Nicely / Daniela Fera / Kan Luo / M Anthony Moody / Hua-Xin Liao / S Munir Alam / Thomas B Kepler / Akshaya Ramesh / Kevin Wiehe / James A Holland / Todd Bradley / Nathan Vandergrift / Kevin O Saunders / Robert Parks / Andrew Foulger / Shi-Mao Xia / Mattia Bonsignori / David C Montefiori / Mark Louder / Amanda Eaton / Sampa Santra / Richard Scearce / Laura Sutherland / Amanda Newman / Hilary Bouton-Verville / Cindy Bowman / Howard Bomze / Feng Gao / Dawn J Marshall / John F Whitesides / Xiaoyan Nie / Garnett Kelsoe / Steven G Reed / Christopher B Fox / Kim Clary / Marguerite Koutsoukos / David Franco / John R Mascola / Stephen C Harrison / Barton F Haynes / Laurent Verkoczy / Abstract: A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report ...A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms that limit the development of CD4-binding site (CD4bs), HCDR3-binder bnAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs antibodies neutralize 7% of HIV-1 strains, recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice EnvB cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env upon receptor editing. In comparison with repetitive Env immunizations, sequential Env administration rescue anergic Env (non-edited) precursor B cells. Thus, stepwise immunization initiates CD4bs-bnAb responses, but immune tolerance mechanisms restrict their development, suggesting that sequential immunogen-based vaccine regimens will likely need to incorporate strategies to expand bnAb precursor pools. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5ukn.cif.gz | 190.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5ukn.ent.gz | 149 KB | Display | PDB format |
PDBx/mmJSON format | 5ukn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5ukn_validation.pdf.gz | 428.2 KB | Display | wwPDB validaton report |
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Full document | 5ukn_full_validation.pdf.gz | 429.9 KB | Display | |
Data in XML | 5ukn_validation.xml.gz | 21.4 KB | Display | |
Data in CIF | 5ukn_validation.cif.gz | 31.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uk/5ukn ftp://data.pdbj.org/pub/pdb/validation_reports/uk/5ukn | HTTPS FTP |
-Related structure data
Related structure data | 9401C 5ukoC 5ukpSC 5ukqC 5ukrC 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
#1: Antibody | Mass: 24497.344 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Macaca mulatta (Rhesus monkey) / Cell line (production host): HEK293F / Production host: Homo sapiens (human) |
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#2: Antibody | Mass: 22736.990 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Macaca mulatta (Rhesus monkey) / Cell line (production host): HEK293F / Production host: Homo sapiens (human) |
#3: Chemical | ChemComp-CL / |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.49 Å3/Da / Density % sol: 50.6 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / Details: 1 M LiCl, 0.1 M citric acid pH 4, 20% PEG 6000 |
-Data collection
Diffraction | Mean temperature: 93 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: Nov 27, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.75→50 Å / Num. obs: 49650 / % possible obs: 99.2 % / Redundancy: 10.4 % / Rsym value: 0.055 / Net I/σ(I): 36.7 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5UKP Resolution: 1.75→42.003 Å / SU ML: 0.16 / Cross valid method: THROUGHOUT / σ(F): 0 / Phase error: 19.27
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.75→42.003 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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