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Yorodumi- PDB-8gje: HIV-1 Env subtype C CZA97.12 SOSIP.664 in complex with 3BNC117 Fab -
+Open data
-Basic information
Entry | Database: PDB / ID: 8gje | ||||||
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Title | HIV-1 Env subtype C CZA97.12 SOSIP.664 in complex with 3BNC117 Fab | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / HIV Envelope / SOSIP / broadly neutralizing antibody / clade C / 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 ...: / 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 Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||
Authors | Ozorowski, G. / Lee, J.H. / Ward, A.B. | ||||||
Funding support | United States, 1items
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Citation | Journal: PLoS Pathog / Year: 2023 Title: Glycan heterogeneity as a cause of the persistent fraction in HIV-1 neutralization. Authors: Rajesh P Ringe / Philippe Colin / Gabriel Ozorowski / Joel D Allen / Anila Yasmeen / Gemma E Seabright / Jeong Hyun Lee / Aleksandar Antanasijevic / Kimmo Rantalainen / Thomas Ketas / John P ...Authors: Rajesh P Ringe / Philippe Colin / Gabriel Ozorowski / Joel D Allen / Anila Yasmeen / Gemma E Seabright / Jeong Hyun Lee / Aleksandar Antanasijevic / Kimmo Rantalainen / Thomas Ketas / John P Moore / Andrew B Ward / Max Crispin / P J Klasse / Abstract: Neutralizing antibodies (NAbs) to multiple epitopes on the HIV-1-envelope glycoprotein (Env) have been isolated from infected persons. The potency of NAbs is measured more often than the size of the ...Neutralizing antibodies (NAbs) to multiple epitopes on the HIV-1-envelope glycoprotein (Env) have been isolated from infected persons. The potency of NAbs is measured more often than the size of the persistent fraction of infectivity at maximum neutralization, which may also influence preventive efficacy of active or passive immunization and the therapeutic outcome of the latter. Many NAbs neutralize HIV-1 CZA97.012, a clone of a Clade-C isolate, to ~100%. But here NAb PGT151, directed to a fusion-peptide epitope, left a persistent fraction of 15%. NAb PGT145, ligating the Env-trimer apex, left no detectable persistent fraction. The divergence in persistent fractions was further analyzed by depletion of pseudoviral populations of the most PGT151- and PGT145-reactive virions. Thereby, neutralization by the non-depleting NAb increased, whereas neutralization by the depleting NAb decreased. Furthermore, depletion by PGT151 increased sensitivity to autologous neutralization by sera from rabbits immunized with soluble native-like CZA97.012 trimer: substantial persistent fractions were reduced. NAbs in these sera target epitopes comprising residue D411 at the V4-β19 transition in a defect of the glycan shield on CZA97.012 Env. NAb binding to affinity-fractionated soluble native-like CZA97.012 trimer differed commensurately with neutralization in analyses by ELISA and surface plasmon resonance. Glycan differences between PGT151- and PGT145-purified trimer fractions were then demonstrated by mass spectrometry, providing one explanation for the differential antigenicity. These differences were interpreted in relation to a new structure at 3.4-Å resolution of the soluble CZA97.012 trimer determined by cryo-electron microscopy. The trimer adopted a closed conformation, refuting apex opening as the cause of reduced PGT145 binding to the PGT151-purified form. The evidence suggests that differences in binding and neutralization after trimer purification or pseudovirus depletion with PGT145 or PGT151 are caused by variation in glycosylation, and that some glycan variants affect antigenicity through direct effects on antibody contacts, whereas others act allosterically. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8gje.cif.gz | 529.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8gje.ent.gz | 430.2 KB | Display | PDB format |
PDBx/mmJSON format | 8gje.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8gje_validation.pdf.gz | 2.8 MB | Display | wwPDB validaton report |
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Full document | 8gje_full_validation.pdf.gz | 2.9 MB | Display | |
Data in XML | 8gje_validation.xml.gz | 77 KB | Display | |
Data in CIF | 8gje_validation.cif.gz | 115.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gj/8gje ftp://data.pdbj.org/pub/pdb/validation_reports/gj/8gje | HTTPS FTP |
-Related structure data
Related structure data | 40088MC 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
-CZA97.12 SOSIP.664 Envelope glycoprotein ... , 2 types, 6 molecules ACDBEF
#1: Protein | Mass: 56995.121 Da / Num. of mol.: 3 Mutation: A501C, and also cleavage site mutations to introduce a furin cleavage site Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: Q994M9 #2: Protein | Mass: 17279.670 Da / Num. of mol.: 3 / Mutation: L535M, I559P, T605C, Q567K Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: Q994M9 |
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-Antibody / Protein , 2 types, 6 molecules HGILJK
#3: Antibody | Mass: 24656.484 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) #4: Protein | Mass: 23022.658 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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-Sugars , 5 types, 60 molecules
#5: 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 #6: Polysaccharide | 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: CZA97.12 SOSIP.664 in complex with 3BNC117 Fab / Type: COMPLEX / Entity ID: #1-#4 / Source: MULTIPLE SOURCES | ||||||||||||||||||||
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Molecular weight | Value: 0.57 MDa / Experimental value: NO | ||||||||||||||||||||
Buffer solution | pH: 7.4 / Details: Detergent added shortly before freezing | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid type: C-flat-2/2 | ||||||||||||||||||||
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 / Nominal magnification: 22500 X / Nominal defocus max: 2700 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 58 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 1142 |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 79261 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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