+Open data
-Basic information
Entry | Database: PDB / ID: 8t4k | |||||||||
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Title | MD64 N332-GT5 SOSIP | |||||||||
Components |
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Keywords | VIRAL PROTEIN / germline targeting / SOSIP / Env / HIV / BG18 / immunogen design | |||||||||
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 / host cell plasma membrane / structural molecule activity / virion membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.6 Å | |||||||||
Authors | Ozorowski, G. / Torres, J.L. / Ward, A.B. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Science / Year: 2024 Title: Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates. Authors: Jon M Steichen / Ivy Phung / Eugenia Salcedo / Gabriel Ozorowski / Jordan R Willis / Sabyasachi Baboo / Alessia Liguori / Christopher A Cottrell / Jonathan L Torres / Patrick J Madden / ...Authors: Jon M Steichen / Ivy Phung / Eugenia Salcedo / Gabriel Ozorowski / Jordan R Willis / Sabyasachi Baboo / Alessia Liguori / Christopher A Cottrell / Jonathan L Torres / Patrick J Madden / Krystal M Ma / Henry J Sutton / Jeong Hyun Lee / Oleksandr Kalyuzhniy / Joel D Allen / Oscar L Rodriguez / Yumiko Adachi / Tina-Marie Mullen / Erik Georgeson / Michael Kubitz / Alison Burns / Shawn Barman / Rohini Mopuri / Amanda Metz / Tasha K Altheide / Jolene K Diedrich / Swati Saha / Kaitlyn Shields / Steven E Schultze / Melissa L Smith / Torben Schiffner / Dennis R Burton / Corey T Watson / Steven E Bosinger / Max Crispin / John R Yates / James C Paulson / Andrew B Ward / Devin Sok / Shane Crotty / William R Schief / Abstract: Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically ...Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo-electron microscopy. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8t4k.cif.gz | 339.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8t4k.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8t4k.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8t4k_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 8t4k_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8t4k_validation.xml.gz | 62 KB | Display | |
Data in CIF | 8t4k_validation.cif.gz | 92.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t4/8t4k ftp://data.pdbj.org/pub/pdb/validation_reports/t4/8t4k | HTTPS FTP |
-Related structure data
Related structure data | 41034MC 8t49C 8t4aC 8t4bC 8t4dC 8t4lC 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
#1: Protein | Mass: 54236.801 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Production host: Homo sapiens (human) #2: Protein | Mass: 18250.541 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: Q2N0S8 #3: Polysaccharide | Source method: isolated from a genetically manipulated source #4: Sugar | ChemComp-NAG / 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: MD64 N332-GT5 SOSIP / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Human immunodeficiency virus 1 |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 2.6 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
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: 36000 X / Nominal defocus max: 2000 nm / Nominal defocus min: 500 nm / Alignment procedure: COMA FREE |
Specimen holder | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 79 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 202102 / Symmetry type: POINT | ||||||||||||||||||||||||
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