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- PDB-5ukr: Structure of unliganded anti-gp120 CD4bs antibody DH522.2 Fab in ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 5ukr | |||||||||||||||
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Title | Structure of unliganded anti-gp120 CD4bs antibody DH522.2 Fab in complex with a gp120 core | |||||||||||||||
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![]() | IMMUNE SYSTEM / HIV gp120 immune system | |||||||||||||||
Function / homology | Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta![]() | |||||||||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||||||||
Method | ![]() ![]() ![]() | |||||||||||||||
![]() | Nicely, N.I. | |||||||||||||||
Funding support | ![]()
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![]() | ![]() 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: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 266 KB | Display | ![]() |
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PDB format | ![]() | 212.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 9401C ![]() 5uknC ![]() 5ukoC ![]() 5ukpSC ![]() 5ukqC ![]() 4r4hS C: citing same article ( S: Starting model for refinement |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Antibody | Mass: 24412.223 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() | ||
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#2: Antibody | Mass: 22873.121 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() | ||
#3: Protein | Mass: 34838.691 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() | ||
#4: Sugar | ChemComp-NAG / #5: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.88 Å3/Da / Density % sol: 57.4 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / Details: 0.1 M MES pH 6.5, 12% PEG 20,000 |
-Data collection
Diffraction | Mean temperature: 93 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Mar 10, 2016 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.7→50 Å / Num. obs: 25631 / % possible obs: 98.6 % / Redundancy: 4.8 % / Rsym value: 0.14 / Net I/σ(I): 13.5 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: The starting model for the Fab component was 5UKP. The starting model for the gp120 component was PDB 4R4H. Resolution: 2.712→49.848 Å / SU ML: 0.36 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 27.38
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.712→49.848 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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