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- EMDB-8083: B41 SOSIP.664 HIV-1 Env trimer in complex with anti-HIV CH235 wk41 Fab -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-8083 | |||||||||
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Title | B41 SOSIP.664 HIV-1 Env trimer in complex with anti-HIV CH235 wk41 Fab | |||||||||
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Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / negative staining / Resolution: 24.0 Å | |||||||||
![]() | Ozorowski G / Ward AB | |||||||||
Funding support | ![]()
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![]() | ![]() 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
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 11.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16 KB 16 KB | Display Display | ![]() |
Images | ![]() | 43.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 77.7 KB | Display | ![]() |
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Full document | ![]() | 76.8 KB | Display | |
Data in XML | ![]() | 494 B | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8078C ![]() 8079C ![]() 8080C ![]() 8081C ![]() 8082C ![]() 5f96C ![]() 5f9oC ![]() 5f9wC C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 2.05 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Complex containing 2 copies of CH235 wk41 anti-HIV Fab bound to a...
Entire | Name: Complex containing 2 copies of CH235 wk41 anti-HIV Fab bound to a trimer of HIV-1 Env B41 SOSIP.664 |
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Components |
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-Supramolecule #1: Complex containing 2 copies of CH235 wk41 anti-HIV Fab bound to a...
Supramolecule | Name: Complex containing 2 copies of CH235 wk41 anti-HIV Fab bound to a trimer of HIV-1 Env B41 SOSIP.664 type: complex / ID: 1 / Parent: 0 |
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Molecular weight | Theoretical: 420 KDa |
-Supramolecule #2: HIV-1 Env B41 SOSIP.664
Supramolecule | Name: HIV-1 Env B41 SOSIP.664 / type: complex / ID: 2 / Parent: 1 Details: Solubilized and stabilized HIV-1 Env trimer from strain B41. Engineered disulfide between A501C and T605C. I559P mutation to stabilize in pre-fusion state. Truncation after D664 to increase ...Details: Solubilized and stabilized HIV-1 Env trimer from strain B41. Engineered disulfide between A501C and T605C. I559P mutation to stabilize in pre-fusion state. Truncation after D664 to increase solubility. Formed with three gp140 subunits. |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-Supramolecule #3: Anti-HIV CH235 wk41 antibody fragment antigen binding
Supramolecule | Name: Anti-HIV CH235 wk41 antibody fragment antigen binding / type: complex / ID: 3 / Parent: 1 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Molecular weight | Theoretical: 50 KDa |
-Experimental details
-Structure determination
Method | negative staining |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.03 mg/mL | |||||||||
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Buffer | pH: 7.4 Component:
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Staining | Type: NEGATIVE / Material: 2% w/v uranyl formate Details: Negatively stained EM samples were prepared on carbon-coated Cu400 grids by applying sample for 10 seconds, blotting, applying 2% w/v uranyl formate for 60 seconds, and blotting again. | |||||||||
Grid | Model: EMS / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Pretreatment - Type: PLASMA CLEANING |
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Electron microscopy
Microscope | FEI TECNAI SPIRIT |
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Details | Collected a tilt series of -50, -40, -30, -20, -10, and 0 degrees. |
Image recording | Film or detector model: TVIPS TEMCAM-F416 (4k x 4k) / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Digitization - Sampling interval: 15.6 µm / Average electron dose: 25.0 e/Å2 |
Electron beam | Acceleration voltage: 120 kV / Electron source: LAB6 |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus min: 1.5 µm / Nominal magnification: 52000 |
Sample stage | Specimen holder model: SIDE ENTRY, EUCENTRIC |
Experimental equipment | ![]() Model: Tecnai Spirit / Image courtesy: FEI Company |