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Yorodumi- PDB-8tq1: HIV-1 BG505 Env SOSIP in complex with bovine Fab Bess4 and non-hu... -
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-Basic information
Entry | Database: PDB / ID: 8tq1 | ||||||
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Title | HIV-1 BG505 Env SOSIP in complex with bovine Fab Bess4 and non-human primate Fab RM20A3 | ||||||
Components |
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Keywords | VIRAL PROTEIN/Immune System / SOSIP / apex / broadly neutralizing antibody / Env / HIV-1 / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex | ||||||
Function / homology | Function and homology information 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 ...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 / apoptotic process / host cell plasma membrane / virion membrane / structural molecule activity / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | Human immunodeficiency virus 1 Macaca mulatta (Rhesus monkey) Bos taurus (cattle) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
Authors | Ozorowski, G. / Lee, W.H. / Ward, A.B. | ||||||
Funding support | United States, 1items
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Citation | Journal: PLoS Pathog / Year: 2024 Title: Immunization of cows with HIV envelope trimers generates broadly neutralizing antibodies to the V2-apex from the ultralong CDRH3 repertoire. Authors: Pilar X Altman / Gabriel Ozorowski / Robyn L Stanfield / Jeremy Haakenson / Michael Appel / Mara Parren / Wen-Hsin Lee / Huldah Sang / Jordan Woehl / Karen Saye-Francisco / Leigh M Sewall / ...Authors: Pilar X Altman / Gabriel Ozorowski / Robyn L Stanfield / Jeremy Haakenson / Michael Appel / Mara Parren / Wen-Hsin Lee / Huldah Sang / Jordan Woehl / Karen Saye-Francisco / Leigh M Sewall / Collin Joyce / Ge Song / Katelyn Porter / Elise Landais / Raiees Andrabi / Ian A Wilson / Andrew B Ward / Waithaka Mwangi / Vaughn V Smider / Dennis R Burton / Devin Sok / Abstract: The generation of broadly neutralizing antibodies (bnAbs) to conserved epitopes on HIV Envelope (Env) is one of the cornerstones of HIV vaccine research. The animal models commonly used for HIV do ...The generation of broadly neutralizing antibodies (bnAbs) to conserved epitopes on HIV Envelope (Env) is one of the cornerstones of HIV vaccine research. The animal models commonly used for HIV do not reliably produce a potent broadly neutralizing serum antibody response, with the exception of cows. Cows have previously produced a CD4 binding site response by homologous prime and boosting with a native-like Env trimer. In small animal models, other engineered immunogens were shown to focus antibody responses to the bnAb V2-apex region of Env. Here, we immunized two groups of cows (n = 4) with two regimens of V2-apex focusing Env immunogens to investigate whether antibody responses could be generated to the V2-apex on Env. Group 1 was immunized with chimpanzee simian immunodeficiency virus (SIV)-Env trimer that shares its V2-apex with HIV, followed by immunization with C108, a V2-apex focusing immunogen, and finally boosted with a cross-clade native-like trimer cocktail. Group 2 was immunized with HIV C108 Env trimer followed by the same HIV trimer cocktail as Group 1. Longitudinal serum analysis showed that one cow in each group developed serum neutralizing antibody responses to the V2-apex. Eight and 11 bnAbs were isolated from Group 1 and Group 2 cows, respectively, and showed moderate breadth and potency. Potent and broad responses in this study developed much later than previous cow immunizations that elicited CD4bs bnAbs responses and required several different immunogens. All isolated bnAbs were derived from the ultralong CDRH3 repertoire. The finding that cow antibodies can target more than one broadly neutralizing epitope on the HIV surface reveals the generality of elongated structures for the recognition of highly glycosylated proteins. The exclusive isolation of ultralong CDRH3 bnAbs, despite only comprising a small percent of the cow repertoire, suggests these antibodies outcompete the long and short CDRH3 antibodies during the bnAb response. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8tq1.cif.gz | 506.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8tq1.ent.gz | 411.2 KB | Display | PDB format |
PDBx/mmJSON format | 8tq1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8tq1_validation.pdf.gz | 2.2 MB | Display | wwPDB validaton report |
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Full document | 8tq1_full_validation.pdf.gz | 2.2 MB | Display | |
Data in XML | 8tq1_validation.xml.gz | 77.7 KB | Display | |
Data in CIF | 8tq1_validation.cif.gz | 117.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tq/8tq1 ftp://data.pdbj.org/pub/pdb/validation_reports/tq/8tq1 | HTTPS FTP |
-Related structure data
Related structure data | 41498MC 8vbjC 8vbkC 8vblC 8vbmC 8vbnC 8vboC 8vbpC 8vbqC 8vbrC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 2 types, 6 molecules AJEBKF
#1: Protein | Mass: 57945.977 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Production host: Homo sapiens (human) / References: UniProt: Q2N0S6 #2: Protein | Mass: 17146.482 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Production host: Homo sapiens (human) / References: UniProt: Q2N0S5 |
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-Antibody , 3 types, 7 molecules CMGDNIH
#3: Antibody | Mass: 13511.111 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Macaca mulatta (Rhesus monkey) / Production host: Homo sapiens (human) #4: Antibody | Mass: 13508.800 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Macaca mulatta (Rhesus monkey) / Production host: Homo sapiens (human) #5: Antibody | | Mass: 17435.293 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Production host: Homo sapiens (human) |
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-Sugars , 4 types, 57 molecules
#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: Sugar | ChemComp-NAG / |
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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 |
-Sample preparation
Component | Name: HIV-1 BG505 SOSIP Env in complex with bovine Bess4 Fab and NHP RM20A3 Fab Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 2.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 130000 X / Nominal defocus max: 1700 nm / Nominal defocus min: 700 nm / Alignment procedure: COMA FREE |
Specimen holder | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 55.5 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 82374 / Symmetry type: POINT | ||||||||||||||||||||||||
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