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- PDB-7kmd: Crystal structure of a HIV-1 clade C isolate Du172.17 HR1.R4.664 ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7kmd | ||||||
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Title | Crystal structure of a HIV-1 clade C isolate Du172.17 HR1.R4.664 Env trimer in complex with human Fabs PGT124 and 35O22 | ||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / HIV / envelope / glycoprotein / prefusion trimer / glycan / HIV-1 GP120 / HIV-1 GP41 / neutralizing antibodies / 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 / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / 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 ...: / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / 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 / host cell plasma membrane / structural molecule activity / virion membrane / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Kumar, S. / Wilson, I.A. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles. Authors: Sonu Kumar / Xiaohe Lin / Timothy Ngo / Benjamin Shapero / Cindy Sou / Joel D Allen / Jeffrey Copps / Lei Zhang / Gabriel Ozorowski / Linling He / Max Crispin / Andrew B Ward / Ian A Wilson / Jiang Zhu / ![]() ![]() Abstract: The immunogenicity of gp41-stabilized HIV-1 BG505 envelope (Env) trimers and nanoparticles (NPs) was recently assessed in mice and rabbits. Here, we combined Env-specific B-cell sorting and ...The immunogenicity of gp41-stabilized HIV-1 BG505 envelope (Env) trimers and nanoparticles (NPs) was recently assessed in mice and rabbits. Here, we combined Env-specific B-cell sorting and repertoire sequencing to identify neutralizing antibodies (NAbs) from immunized animals. A panel of mouse NAbs was isolated from mice immunized with a 60-meric I3-01 NP presenting 20 stabilized trimers. Three mouse NAbs potently neutralized BG505.T332N by recognizing a glycan epitope centered in the C3/V4 region on BG505 Env, as revealed by electron microscopy (EM), X-ray crystallography, and epitope mapping. A set of rabbit NAbs was isolated from rabbits immunized with a soluble trimer and a 24-meric ferritin NP presenting 8 trimers. Neutralization assays against BG505.T332N variants confirmed that potent rabbit NAbs targeted previously described glycan holes on BG505 Env and accounted for a significant portion of the autologous NAb response in both the trimer and ferritin NP groups. Last, we examined NAb responses that were induced by non-BG505 Env immunogens. We determined a 3.4-Å-resolution crystal structure for the clade C transmitted/founder (T/F) Du172.17 Env with a redesigned heptad repeat 1 (HR1) bend in gp41. This clade C Env, in a soluble trimer form and in a multivalent form with 8 trimers attached to ferritin NP, and the gp41-stabilized clade A Q482-d12 Env trimer elicited distinct NAb responses in rabbits, with notable differences in neutralization breadth. Although eliciting a broad NAb response remains a major challenge, our study provides valuable information on an HIV-1 vaccine design strategy that combines gp41 stabilization and NP display. Self-assembling protein nanoparticles (NPs) presenting BG505 envelope (Env) trimers can elicit tier 2 HIV-1-neutralizing antibody (NAb) responses more effectively than soluble trimers. In the present study, monoclonal NAbs were isolated from previously immunized mice and rabbits for structural and functional analyses, which revealed that potent mouse NAbs recognize the C3/V4 region and small NP-elicited rabbit NAbs primarily target known glycan holes on BG505 Env. This study validates the gp41 stabilization strategy for HIV-1 Env vaccine design and highlights the challenge in eliciting a broad NAb response. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 324.4 KB | Display | ![]() |
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PDB format | ![]() | 256 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 3.3 MB | Display | ![]() |
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Full document | ![]() | 3.3 MB | Display | |
Data in XML | ![]() | 54.6 KB | Display | |
Data in CIF | ![]() | 73.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7kkzC ![]() 7klcC ![]() 4r26S ![]() 4toyS ![]() 5cezS S: Starting model for refinement 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
-Protein , 2 types, 2 molecules AH
#1: Protein | Mass: 26171.520 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#6: Protein | Mass: 25460.508 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Envelope glycoprotein ... , 2 types, 2 molecules GT
#3: Protein | Mass: 54118.543 Da / Num. of mol.: 1 / Fragment: UNP residues 31-505 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#4: Protein | Mass: 15631.747 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Antibody , 2 types, 2 molecules EL
#2: Antibody | Mass: 23318.824 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#5: Antibody | Mass: 23056.605 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Sugars , 7 types, 20 molecules ![](data/chem/img/NAG.gif)
#7: Polysaccharide | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)]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 | ||||||||||
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#8: Polysaccharide | Source method: isolated from a genetically manipulated source #9: 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 #10: Polysaccharide | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)]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 #11: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]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 #12: Polysaccharide | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(6-8)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)]2-acetamido-2-deoxy-beta-D-glucopyranose | Type: oligosaccharide / Mass: 1155.068 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source #13: Sugar | ChemComp-NAG / |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 4.39 Å3/Da / Density % sol: 72.01 % |
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Crystal grow | Temperature: 293.15 K / Method: vapor diffusion, sitting drop / Details: 0.1M Tris pH=8.4, 25%(v/v) PEG400 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Mar 29, 2019 |
Radiation | Monochromator: double crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.033 Å / Relative weight: 1 |
Reflection | Resolution: 3.39→50 Å / Num. obs: 38788 / % possible obs: 97.6 % / Redundancy: 6.4 % / Biso Wilson estimate: 92.5907504709 Å2 / CC1/2: 0.85 / Net I/σ(I): 8.6 |
Reflection shell | Resolution: 3.4→3.46 Å / Num. unique obs: 1614 / CC1/2: 0.45 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: PDB entries 5CEZ, 4TOY, 4R26 Resolution: 3.39228580771→49.5301719699 Å / SU ML: 0.574407368599 / Cross valid method: FREE R-VALUE / σ(F): 1.33790597134 / Phase error: 34.8287325509 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 113.176596028 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.39228580771→49.5301719699 Å
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Refine LS restraints |
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LS refinement shell |
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