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Yorodumi- PDB-6cue: Cryo-EM structure at 4.0 A resolution of vaccine-elicited antibod... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6cue | |||||||||
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Title | Cryo-EM structure at 4.0 A resolution of vaccine-elicited antibody vFP7.04 in complex with HIV-1 Env BG505 DS-SOSIP, and antibodies VRC03 and PGT122 | |||||||||
Components |
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Keywords | VIRAL PROTEIN / HIV-1 Env / BG505 SOSIP / fusion peptide / VRC03 / PGT122 / vFP7.04 | |||||||||
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 / structural molecule activity / virion membrane / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 Mus musculus (house mouse) Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | |||||||||
Authors | Acharya, P. / Carragher, B. / Potter, C.S. / Kwong, P.D. | |||||||||
Citation | Journal: PLoS Pathog / Year: 2018 Title: Complete functional mapping of infection- and vaccine-elicited antibodies against the fusion peptide of HIV. Authors: Adam S Dingens / Priyamvada Acharya / Hugh K Haddox / Reda Rawi / Kai Xu / Gwo-Yu Chuang / Hui Wei / Baoshan Zhang / John R Mascola / Bridget Carragher / Clinton S Potter / Julie Overbaugh / ...Authors: Adam S Dingens / Priyamvada Acharya / Hugh K Haddox / Reda Rawi / Kai Xu / Gwo-Yu Chuang / Hui Wei / Baoshan Zhang / John R Mascola / Bridget Carragher / Clinton S Potter / Julie Overbaugh / Peter D Kwong / Jesse D Bloom / Abstract: Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. ...Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutralizing antibody responses in a variety of animal models using immunogens based on the epitope of bnAb VRC34.01. The VRC34.01 antibody, which was elicited by natural human infection, targets the N terminus of the Env fusion peptide, a critical component of the virus entry machinery. Here we precisely characterize the functional epitopes of VRC34.01 and two vaccine-elicited murine antibodies by mapping all single amino-acid mutations to the BG505 Env that affect viral neutralization. While escape from VRC34.01 occurred via mutations in both fusion peptide and distal interacting sites of the Env trimer, escape from the vaccine-elicited antibodies was mediated predominantly by mutations in the fusion peptide. Cryo-electron microscopy of four vaccine-elicited antibodies in complex with Env trimer revealed focused recognition of the fusion peptide and provided a structural basis for development of neutralization breadth. Together, these functional and structural data suggest that the breadth of vaccine-elicited antibodies targeting the fusion peptide can be enhanced by specific interactions with additional portions of Env. Thus, our complete maps of viral escape both delineate pathways of resistance to these fusion peptide-directed antibodies and provide a strategy to improve the breadth or potency of future vaccine-induced antibodies against Env's fusion peptide. | |||||||||
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 | 6cue.cif.gz | 703.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6cue.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 6cue.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6cue_validation.pdf.gz | 3.2 MB | Display | wwPDB validaton report |
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Full document | 6cue_full_validation.pdf.gz | 3.2 MB | Display | |
Data in XML | 6cue_validation.xml.gz | 96.6 KB | Display | |
Data in CIF | 6cue_validation.cif.gz | 153.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cu/6cue ftp://data.pdbj.org/pub/pdb/validation_reports/cu/6cue | HTTPS FTP |
-Related structure data
Related structure data | 7621MC 7622C 6cufC 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
-Envelope glycoprotein ... , 2 types, 6 molecules c2C1Dd
#1: Protein | Mass: 52986.969 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: 17162.525 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: Q2N0S7 |
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-Protein , 2 types, 6 molecules 3Hh5Mm
#3: Protein | Mass: 13152.787 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human) #5: Protein | Mass: 14838.731 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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-Antibody , 4 types, 12 molecules 4Ll6Nn7Qq8Rr
#4: Antibody | Mass: 12256.805 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human) #6: Antibody | Mass: 11591.728 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #7: Antibody | Mass: 14639.500 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #8: Antibody | Mass: 11386.774 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 , 6 types, 42 molecules
#9: 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 #10: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #11: Polysaccharide | Source method: isolated from a genetically manipulated source #12: Polysaccharide | Source method: isolated from a genetically manipulated source #13: Polysaccharide | Source method: isolated from a genetically manipulated source #14: Sugar | |
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-Details
Has protein modification | 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
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7 | ||||||||||||||||||||||||||||||||||||
Specimen | Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||
Vitrification | Instrument: SPOTITON / 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 / Calibrated magnification: 105000 X / Calibrated defocus min: 1500 nm / Calibrated defocus max: 3000 nm |
Specimen holder | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 53.11 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 978 |
Image scans | Movie frames/image: 40 / Used frames/image: 1-40 |
-Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement | ||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 152206 | ||||||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 64580 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | B value: 142 / Protocol: FLEXIBLE FIT / Space: REAL / Target criteria: Correlation Coefficient | ||||||||||||||||||||||||||||
Refinement | Highest resolution: 4 Å |