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Yorodumi- PDB-7tfn: Cryo-EM structure of CD4bs antibody Ab1303 in complex with HIV-1 ... -
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-Basic information
Entry | Database: PDB / ID: 7tfn | |||||||||
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Title | Cryo-EM structure of CD4bs antibody Ab1303 in complex with HIV-1 Env trimer BG505 SOSIP.664 | |||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 Env / neutralizing antibody / CD4 binding site antibody / 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 / membrane => GO:0016020 / 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 / membrane => GO:0016020 / 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 / virion membrane / structural molecule activity / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 Macaca mulatta (Rhesus monkey) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | |||||||||
Authors | Yang, Z. / Bjorkman, P.J. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nat Commun / Year: 2022 Title: Neutralizing antibodies induced in immunized macaques recognize the CD4-binding site on an occluded-open HIV-1 envelope trimer. Authors: Zhi Yang / Kim-Marie A Dam / Michael D Bridges / Magnus A G Hoffmann / Andrew T DeLaitsch / Harry B Gristick / Amelia Escolano / Rajeev Gautam / Malcolm A Martin / Michel C Nussenzweig / ...Authors: Zhi Yang / Kim-Marie A Dam / Michael D Bridges / Magnus A G Hoffmann / Andrew T DeLaitsch / Harry B Gristick / Amelia Escolano / Rajeev Gautam / Malcolm A Martin / Michel C Nussenzweig / Wayne L Hubbell / Pamela J Bjorkman / Abstract: Broadly-neutralizing antibodies (bNAbs) against HIV-1 Env can protect from infection. We characterize Ab1303 and Ab1573, heterologously-neutralizing CD4-binding site (CD4bs) antibodies, isolated from ...Broadly-neutralizing antibodies (bNAbs) against HIV-1 Env can protect from infection. We characterize Ab1303 and Ab1573, heterologously-neutralizing CD4-binding site (CD4bs) antibodies, isolated from sequentially-immunized macaques. Ab1303/Ab1573 binding is observed only when Env trimers are not constrained in the closed, prefusion conformation. Fab-Env cryo-EM structures show that both antibodies recognize the CD4bs on Env trimer with an 'occluded-open' conformation between closed, as targeted by bNAbs, and fully-open, as recognized by CD4. The occluded-open Env trimer conformation includes outwardly-rotated gp120 subunits, but unlike CD4-bound Envs, does not exhibit V1V2 displacement, 4-stranded gp120 bridging sheet, or co-receptor binding site exposure. Inter-protomer distances within trimers measured by double electron-electron resonance spectroscopy suggest an equilibrium between occluded-open and closed Env conformations, consistent with Ab1303/Ab1573 binding stabilizing an existing conformation. Studies of Ab1303/Ab1573 demonstrate that CD4bs neutralizing antibodies that bind open Env trimers can be raised by immunization, thereby informing immunogen design and antibody therapeutic efforts. | |||||||||
History |
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-Structure visualization
Movie |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7tfn.cif.gz | 564.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7tfn.ent.gz | 453.4 KB | Display | PDB format |
PDBx/mmJSON format | 7tfn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7tfn_validation.pdf.gz | 1.8 MB | Display | wwPDB validaton report |
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Full document | 7tfn_full_validation.pdf.gz | 1.8 MB | Display | |
Data in XML | 7tfn_validation.xml.gz | 72 KB | Display | |
Data in CIF | 7tfn_validation.cif.gz | 107.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tf/7tfn ftp://data.pdbj.org/pub/pdb/validation_reports/tf/7tfn | HTTPS FTP |
-Related structure data
Related structure data | 25877MC 7ryuC 7ryvC 7tfoC 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 BG505 SOSIP.664 - ... , 2 types, 6 molecules ABCXYZ
#1: Protein | Mass: 54064.344 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: A0A6H1VH54 #4: Protein | Mass: 17146.482 Da / Num. of mol.: 3 / Fragment: UNP residues 509-661 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: Q2N0S6 |
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-Antibody , 2 types, 6 molecules HIPJLQ
#2: Antibody | Mass: 25338.176 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Macaca mulatta (Rhesus monkey) / Cell line (production host): Expi293F / Production host: Homo sapiens (human) #3: Antibody | Mass: 23419.977 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Macaca mulatta (Rhesus monkey) / Cell line (production host): Expi293F / Production host: Homo sapiens (human) |
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-Sugars , 7 types, 25 molecules
#5: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]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 | ||||||||||
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#6: 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 #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 | alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-6)-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 #9: Polysaccharide | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-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 #10: Sugar | ChemComp-NAG / #11: Sugar | ChemComp-MAN / | |
-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: Cryo-EM map of Ab1303 in complex with BG505 SOSIP.664 Env trimer (local resolution refined) Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: Expi293F |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1400 nm / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 386825 / Symmetry type: POINT |
Refinement | Highest resolution: 4 Å |