+Open data
-Basic information
Entry | Database: PDB / ID: 7rsn | ||||||||||||
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Title | AMC018 SOSIP.v4.2 in complex with PGV04 Fab | ||||||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / HIV / Env / antibody / bnAb / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||||||||
Biological species | Human immunodeficiency virus 1 Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.49 Å | ||||||||||||
Authors | Cottrell, C.A. / Ward, A.B. | ||||||||||||
Funding support | United States, 3items
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Citation | Journal: J Virol / Year: 2022 Title: The Glycan Hole Area of HIV-1 Envelope Trimers Contributes Prominently to the Induction of Autologous Neutralization. Authors: Anna Schorcht / Christopher A Cottrell / Pavel Pugach / Rajesh P Ringe / Alvin X Han / Joel D Allen / Tom L G M van den Kerkhof / Gemma E Seabright / Edith E Schermer / Thomas J Ketas / ...Authors: Anna Schorcht / Christopher A Cottrell / Pavel Pugach / Rajesh P Ringe / Alvin X Han / Joel D Allen / Tom L G M van den Kerkhof / Gemma E Seabright / Edith E Schermer / Thomas J Ketas / Judith A Burger / Jelle van Schooten / Celia C LaBranche / Gabriel Ozorowski / Natalia de Val / Daniel L V Bader / Hanneke Schuitemaker / Colin A Russell / David C Montefiori / Marit J van Gils / Max Crispin / P J Klasse / Andrew B Ward / John P Moore / Rogier W Sanders / Abstract: The human immunodeficiency virus type 1 (HIV-1) trimeric envelope glycoprotein (Env) is heavily glycosylated, creating a dense glycan shield that protects the underlying peptidic surface from ...The human immunodeficiency virus type 1 (HIV-1) trimeric envelope glycoprotein (Env) is heavily glycosylated, creating a dense glycan shield that protects the underlying peptidic surface from antibody recognition. The absence of conserved glycans, due to missing potential N-linked glycosylation sites (PNGS), can result in strain-specific, autologous neutralizing antibody (NAb) responses. Here, we sought to gain a deeper understanding of the autologous neutralization by introducing holes in the otherwise dense glycan shields of the AMC011 and AMC016 SOSIP trimers. Specifically, when we knocked out the N130 and N289 glycans, which are absent from the well-characterized B41 SOSIP trimer, we observed stronger autologous NAb responses. We also analyzed the highly variable NAb responses induced in rabbits by diverse SOSIP trimers from subtypes A, B, and C. Statistical analysis, using linear regression, revealed that the cumulative area exposed on a trimer by glycan holes correlates with the magnitude of the autologous NAb response. Forty years after the first description of HIV-1, the search for a protective vaccine is still ongoing. The sole target for antibodies that can neutralize the virus are the trimeric envelope glycoproteins (Envs) located on the viral surface. The glycoprotein surface is covered with glycans that shield off the underlying protein components from recognition by the immune system. However, the Env trimers of some viral strains have holes in the glycan shield. Immunized animals developed antibodies against such glycan holes. These antibodies are generally strain specific. Here, we sought to gain a deeper understanding of what drives these specific immune responses. First, we show that strain-specific neutralizing antibody responses can be increased by creating artificial holes in the glycan shield. Second, when studying a diverse set of Env trimers with different characteristics, we found that the surface area of the glycan holes contributes prominently to the induction of strain-specific neutralizing antibodies. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7rsn.cif.gz | 487.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7rsn.ent.gz | 412.4 KB | Display | PDB format |
PDBx/mmJSON format | 7rsn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7rsn_validation.pdf.gz | 2.4 MB | Display | wwPDB validaton report |
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Full document | 7rsn_full_validation.pdf.gz | 2.5 MB | Display | |
Data in XML | 7rsn_validation.xml.gz | 77.2 KB | Display | |
Data in CIF | 7rsn_validation.cif.gz | 113.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rs/7rsn ftp://data.pdbj.org/pub/pdb/validation_reports/rs/7rsn | HTTPS FTP |
-Related structure data
Related structure data | 24675MC 7rsoC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 3 types, 9 molecules ACGBDILJK
#1: Protein | Mass: 54705.789 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Cell line (production host): HEK293F / Production host: Homo sapiens (human) #2: Protein | Mass: 17152.566 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Cell line (production host): HEK293F / Production host: Homo sapiens (human) #4: Protein | Mass: 23073.822 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293F / Production host: Homo sapiens (human) |
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-Antibody , 1 types, 3 molecules HEF
#3: Antibody | Mass: 24759.861 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293F / Production host: Homo sapiens (human) |
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-Sugars , 5 types, 48 molecules
#5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: 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 #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: AMC018 SOSIP.v4.2 in complex with PGV04 Fab / Type: COMPLEX / Entity ID: #1-#4 / Source: MULTIPLE SOURCES |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Human immunodeficiency virus 1 |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: HEK293F |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: HOMEMADE PLUNGER / Cryogen name: ETHANE |
-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 |
Specimen holder | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 7 sec. / Electron dose: 26.6 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 3916 |
Image scans | Movie frames/image: 35 |
-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: 3.49 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 150333 / Symmetry type: POINT | ||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |