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Yorodumi- PDB-8g4t: Vaccine-elicited human antibody 2C09 in complex with HIV-1 envelo... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8g4t | ||||||
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Title | Vaccine-elicited human antibody 2C09 in complex with HIV-1 envelope trimer BG505 DS-SOSIP | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / antibody-antigen complex vaccine-elicited antibody fusion peptide strain specific / ANTIVIRAL 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 / virus-mediated perturbation of host defense response / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / 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 / virus-mediated perturbation of host defense response / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / structural molecule activity / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | Human immunodeficiency virus 1 Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.81 Å | ||||||
Authors | Wang, S. / Kwong, P.D. | ||||||
Funding support | United States, 1items
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Citation | Journal: Cell Rep / Year: 2023 Title: HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide. Authors: Shuishu Wang / Flavio Matassoli / Baoshan Zhang / Tracy Liu / Chen-Hsiang Shen / Tatsiana Bylund / Timothy Johnston / Amy R Henry / I-Ting Teng / Prabhanshu Tripathi / Jordan E Becker / ...Authors: Shuishu Wang / Flavio Matassoli / Baoshan Zhang / Tracy Liu / Chen-Hsiang Shen / Tatsiana Bylund / Timothy Johnston / Amy R Henry / I-Ting Teng / Prabhanshu Tripathi / Jordan E Becker / Anita Changela / Ridhi Chaudhary / Cheng Cheng / Martin Gaudinski / Jason Gorman / Darcy R Harris / Myungjin Lee / Nicholas C Morano / Laura Novik / Sijy O'Dell / Adam S Olia / Danealle K Parchment / Reda Rawi / Jesmine Roberts-Torres / Tyler Stephens / Yaroslav Tsybovsky / Danyi Wang / David J Van Wazer / Tongqing Zhou / Nicole A Doria-Rose / Richard A Koup / Lawrence Shapiro / Daniel C Douek / Adrian B McDermott / Peter D Kwong / Abstract: Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers ...Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the "DS-SOSIP"-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for donor-lineage.clone), that neutralize the autologous tier-2 strain, BG505. Though derived from distinct lineages, these antibodies form a reproducible antibody class that targets the HIV-1 fusion peptide. Both antibodies are highly strain specific, which we attribute to their partial recognition of a BG505-specific glycan hole and to their binding requirements for a few BG505-specific residues. Prefusion-stabilized envelope trimers can thus elicit autologous tier-2 neutralizing antibodies in humans, with initially identified neutralizing antibodies recognizing the fusion-peptide site of vulnerability. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8g4t.cif.gz | 522.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8g4t.ent.gz | 433.9 KB | Display | PDB format |
PDBx/mmJSON format | 8g4t.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/g4/8g4t ftp://data.pdbj.org/pub/pdb/validation_reports/g4/8g4t | HTTPS FTP |
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-Related structure data
Related structure data | 29731MC 8g4mC 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
-Envelope glycoprotein BG505 DS-SOSIP ... , 2 types, 6 molecules ABFCGI
#1: Protein | Mass: 17162.525 Da / Num. of mol.: 3 / Mutation: BG505 DS-SOSIP mutations Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Cell line (production host): CHO-DG44 / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: Q2N0S7 #2: Protein | Mass: 52986.969 Da / Num. of mol.: 3 / Mutation: BG505 DS-SOSIP mutations Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Cell line (production host): CHO-DG44 / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: Q2N0S6 |
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-Antibody , 2 types, 6 molecules HDJLEK
#3: Antibody | Mass: 24761.762 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Expi293F / Production host: Homo sapiens (human) #4: Antibody | Mass: 23281.764 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Expi293F / Production host: Homo sapiens (human) |
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-Sugars , 5 types, 60 molecules
#5: Polysaccharide | Source method: isolated from a genetically manipulated source #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 | Y |
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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 envelope trimer in complex with three copies of antibody Fab Type: COMPLEX / Entity ID: #1-#4 / Source: MULTIPLE SOURCES |
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Buffer solution | pH: 7.4 / Details: PBS + 0.1mM DDM |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid type: Quantifoil R2/2 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / 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 FIELDBright-field microscopy / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm |
Image recording | Electron dose: 58 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software |
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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: 2.81 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 445733 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT | ||||||||||||||||||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 110.55 Å2 | ||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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