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- PDB-5f9o: Crystal structure of broadly neutralizing VH1-46 germline-derived... -
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Open data
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Basic information
Entry | Database: PDB / ID: 5f9o | ||||||
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Title | Crystal structure of broadly neutralizing VH1-46 germline-derived CD4-binding site-directed antibody CH235.09 in complex with HIV-1 clade A/E 93TH057 gp120 | ||||||
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Function / homology | ![]() | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ![]() ![]() | ||||||
![]() | Joyce, M.G. / Mascola, J.R. / Kwong, P.D. | ||||||
![]() | ![]() Title: Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Authors: Mattia Bonsignori / Tongqing Zhou / Zizhang Sheng / Lei Chen / Feng Gao / M Gordon Joyce / Gabriel Ozorowski / Gwo-Yu Chuang / Chaim A Schramm / Kevin Wiehe / S Munir Alam / Todd Bradley / ...Authors: Mattia Bonsignori / Tongqing Zhou / Zizhang Sheng / Lei Chen / Feng Gao / M Gordon Joyce / Gabriel Ozorowski / Gwo-Yu Chuang / Chaim A Schramm / Kevin Wiehe / S Munir Alam / Todd Bradley / Morgan A Gladden / Kwan-Ki Hwang / Sheelah Iyengar / Amit Kumar / Xiaozhi Lu / Kan Luo / Michael C Mangiapani / Robert J Parks / Hongshuo Song / Priyamvada Acharya / Robert T Bailer / Allen Cao / Aliaksandr Druz / Ivelin S Georgiev / Young D Kwon / Mark K Louder / Baoshan Zhang / Anqi Zheng / Brenna J Hill / Rui Kong / Cinque Soto / / James C Mullikin / Daniel C Douek / David C Montefiori / Michael A Moody / George M Shaw / Beatrice H Hahn / Garnett Kelsoe / Peter T Hraber / Bette T Korber / Scott D Boyd / Andrew Z Fire / Thomas B Kepler / Lawrence Shapiro / Andrew B Ward / John R Mascola / Hua-Xin Liao / Peter D Kwong / Barton F Haynes / ![]() Abstract: Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling ...Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a VH1-46-derived antibody lineage that matured to neutralize 90% of HIV-1 isolates. Structures of lineage antibodies CH235 (week 41 from time-of-infection, 18% breadth), CH235.9 (week 152, 77%), and CH235.12 (week 323, 90%) demonstrated the maturing epitope to focus on the conformationally invariant portion of the CD4bs. Similarities between CH235 lineage and five unrelated CD4bs lineages in epitope focusing, length-of-time to develop breadth, and extraordinary level of somatic hypermutation suggested commonalities in maturation among all CD4bs antibodies. Fortunately, the required CH235-lineage hypermutation appeared substantially guided by the intrinsic mutability of the VH1-46 gene, which closely resembled VH1-2. We integrated our CH235-lineage findings with a second broadly neutralizing lineage and HIV-1 co-evolution to suggest a vaccination strategy for inducing both lineages. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 326.9 KB | Display | ![]() |
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PDB format | ![]() | 267.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 8078C ![]() 8079C ![]() 8080C ![]() 8081C ![]() 8082C ![]() 8083C ![]() 5f96C ![]() 5f9wC C: citing same article ( |
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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
-Antibody , 2 types, 2 molecules HL
#2: Antibody | Mass: 25218.555 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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#3: Antibody | Mass: 23532.176 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
-Protein / Sugars , 2 types, 13 molecules G![](data/chem/img/NAG.gif)
![](data/chem/img/NAG.gif)
#1: Protein | Mass: 39082.320 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
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#4: Sugar | ChemComp-NAG / ![]() |
-Non-polymers , 3 types, 463 molecules ![](data/chem/img/EPE.gif)
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![](data/chem/img/HOH.gif)
#5: Chemical | ![]() #6: Chemical | ChemComp-15P / | ![]() #7: Water | ChemComp-HOH / | ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.77 Å3/Da / Density % sol: 55.52 % |
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Crystal grow![]() | Temperature: 293 K / Method: vapor diffusion, hanging drop Details: 9% (w/v) PEG8000, 19% (w/v) of PEG400, 0.1 M HEPES pH 7.5 PH range: 7.5 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: RAYONIX MX300-HS / Detector: CCD / Date: Aug 23, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength![]() |
Reflection | Resolution: 1.8599→50 Å / Num. obs: 73935 / % possible obs: 89.7 % / Redundancy: 3.4 % / Net I/σ(I): 7.06 |
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Processing
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Refinement | Resolution: 1.86→35.815 Å / SU ML: 0.19 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 25.48 / 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: 1.86→35.815 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 3.2729 Å / Origin y: -23.8821 Å / Origin z: -27.8733 Å
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Refinement TLS group | Selection details: all |