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- PDB-7n65: Complex structure of HIV superinfection Fab QA013.2 and BG505.SOS... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7n65 | ||||||
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Title | Complex structure of HIV superinfection Fab QA013.2 and BG505.SOSIP.664 | ||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 Envelope / superinfection antibody QA013.2 / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | ![]() positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / viral process / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / membrane => GO:0016020 / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response ...positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / viral process / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / membrane => GO:0016020 / viral protein processing / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / apoptotic process / host cell plasma membrane / structural molecule activity / virion membrane / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.15 Å | ||||||
![]() | Mangala Prasad, V. / Shipley, M.M. / Overbaugh, J.M. / Lee, K.K. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Functional development of a V3/glycan-specific broadly neutralizing antibody isolated from a case of HIV superinfection. Authors: Mackenzie M Shipley / Vidya Mangala Prasad / Laura E Doepker / Adam Dingens / Duncan K Ralph / Elias Harkins / Amrit Dhar / Dana Arenz / Vrasha Chohan / Haidyn Weight / Kishor Mandaliya / ...Authors: Mackenzie M Shipley / Vidya Mangala Prasad / Laura E Doepker / Adam Dingens / Duncan K Ralph / Elias Harkins / Amrit Dhar / Dana Arenz / Vrasha Chohan / Haidyn Weight / Kishor Mandaliya / Jesse D Bloom / Frederick A Matsen / Kelly K Lee / Julie M Overbaugh / ![]() ![]() Abstract: Stimulating broadly neutralizing antibodies (bnAbs) directly from germline remains a barrier for HIV vaccines. HIV superinfection elicits bnAbs more frequently than single infection, providing clues ...Stimulating broadly neutralizing antibodies (bnAbs) directly from germline remains a barrier for HIV vaccines. HIV superinfection elicits bnAbs more frequently than single infection, providing clues of how to elicit such responses. We used longitudinal antibody sequencing and structural studies to characterize bnAb development from a superinfection case. BnAb QA013.2 bound initial and superinfecting viral Env, despite its probable naive progenitor only recognizing the superinfecting strain, suggesting both viruses influenced this lineage. A 4.15 Å cryo-EM structure of QA013.2 bound to native-like trimer showed recognition of V3 signatures (N301/N332 and GDIR). QA013.2 relies less on CDRH3 and more on framework and CDRH1 for affinity and breadth compared to other V3/glycan-specific bnAbs. Antigenic profiling revealed that viral escape was achieved by changes in the structurally-defined epitope and by mutations in V1. These results highlight shared and novel properties of QA013.2 relative to other V3/glycan-specific bnAbs in the setting of sequential, diverse antigens. | ||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 486 KB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 24195MC M: map data used to model this data 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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Components
-Envelope glycoprotein ... , 2 types, 6 molecules AEIBFJ
#1: Protein | Mass: 56846.613 Da / Num. of mol.: 3 / Mutation: T332N Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 18245.830 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Antibody , 2 types, 6 molecules CGKDHL
#3: Antibody | Mass: 14384.085 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #4: Antibody | Mass: 11189.263 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Sugars , 8 types, 63 molecules ![](data/chem/img/NAG.gif)
![](data/chem/img/MAN.gif)
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#5: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #6: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #7: Polysaccharide | Source method: isolated from a genetically manipulated source #8: Polysaccharide | Source method: isolated from a genetically manipulated source #9: Polysaccharide | Source method: isolated from a genetically manipulated source #10: Polysaccharide | Source method: isolated from a genetically manipulated source #11: Sugar | ChemComp-NAG / #12: Sugar | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Complex of HIV-1 envelope protein with super-infection Fab QA013.2 Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT | |||||||||||||||
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Molecular weight | Value: 0.5 MDa / Experimental value: NO | |||||||||||||||
Source (natural) |
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Source (recombinant) | Organism: ![]() | |||||||||||||||
Buffer solution | pH: 7.4 / Details: 1X PBS at pH 7.4, made fresh. | |||||||||||||||
Buffer component | Name: Phosphate buffer saline | |||||||||||||||
Specimen | Conc.: 0.05 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Monodisperse sample in PBS | |||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: PELCO Ultrathin Carbon with Lacey Carbon | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: 3ul sample volume, blotted for 3-4 seconds |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS / Details: Preliminary grid screening was performed manually |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 110000 X / Nominal defocus max: 3500 nm / Nominal defocus min: 1700 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 10 sec. / Electron dose: 44 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 6475 |
Image scans | Movie frames/image: 50 |
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Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1082742 / Details: LOG picker | ||||||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.15 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 113470 / Algorithm: FOURIER SPACE / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT Details: Rigid body fitting in Chimera, followed by real space refinement in Phenix using reference model restraints | ||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 5ACO | ||||||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 124.29 Å2 | ||||||||||||||||||||||||||||
Refine LS restraints |
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