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Yorodumi- PDB-6cdo: Structure of vaccine-elicited HIV-1 neutralizing antibody vFP16.0... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6cdo | ||||||
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Title | Structure of vaccine-elicited HIV-1 neutralizing antibody vFP16.02 in complex with HIV-1 fusion peptide residue 512-519 | ||||||
Components |
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Keywords | IMMUNE SYSTEM / Neutralizing / antibody / fusion peptide / 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 / 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 / plasma membrane Similarity search - Function | ||||||
Biological species | Mus musculus (house mouse) Human immunodeficiency virus 1 | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.099 Å | ||||||
Authors | Xu, K. / Liu, K. / Kwong, P.D. | ||||||
Citation | Journal: Nat Med / Year: 2018 Title: Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1. Authors: Kai Xu / Priyamvada Acharya / Rui Kong / Cheng Cheng / Gwo-Yu Chuang / Kevin Liu / Mark K Louder / Sijy O'Dell / Reda Rawi / Mallika Sastry / Chen-Hsiang Shen / Baoshan Zhang / Tongqing Zhou ...Authors: Kai Xu / Priyamvada Acharya / Rui Kong / Cheng Cheng / Gwo-Yu Chuang / Kevin Liu / Mark K Louder / Sijy O'Dell / Reda Rawi / Mallika Sastry / Chen-Hsiang Shen / Baoshan Zhang / Tongqing Zhou / Mangaiarkarasi Asokan / Robert T Bailer / Michael Chambers / Xuejun Chen / Chang W Choi / Venkata P Dandey / Nicole A Doria-Rose / Aliaksandr Druz / Edward T Eng / S Katie Farney / Kathryn E Foulds / Hui Geng / Ivelin S Georgiev / Jason Gorman / Kurt R Hill / Alexander J Jafari / Young D Kwon / Yen-Ting Lai / Thomas Lemmin / Krisha McKee / Tiffany Y Ohr / Li Ou / Dongjun Peng / Ariana P Rowshan / Zizhang Sheng / John-Paul Todd / Yaroslav Tsybovsky / Elise G Viox / Yiran Wang / Hui Wei / Yongping Yang / Amy F Zhou / Rui Chen / Lu Yang / Diana G Scorpio / Adrian B McDermott / Lawrence Shapiro / Bridget Carragher / Clinton S Potter / John R Mascola / Peter D Kwong / Abstract: A central goal of HIV-1 vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N- ...A central goal of HIV-1 vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N-terminal residues of the fusion peptide, a critical component of the viral entry machinery and the epitope of antibodies elicited by HIV-1 infection, through immunization with fusion peptide-coupled carriers and prefusion stabilized envelope trimers, induces cross-clade neutralizing responses. In mice, these immunogens elicited monoclonal antibodies capable of neutralizing up to 31% of a cross-clade panel of 208 HIV-1 strains. Crystal and cryoelectron microscopy structures of these antibodies revealed fusion peptide conformational diversity as a molecular explanation for the cross-clade neutralization. Immunization of guinea pigs and rhesus macaques induced similarly broad fusion peptide-directed neutralizing responses, suggesting translatability. The N terminus of the HIV-1 fusion peptide is thus a promising target of vaccine efforts aimed at eliciting broadly neutralizing antibodies. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6cdo.cif.gz | 105.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6cdo.ent.gz | 82.9 KB | Display | PDB format |
PDBx/mmJSON format | 6cdo.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6cdo_validation.pdf.gz | 4.2 MB | Display | wwPDB validaton report |
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Full document | 6cdo_full_validation.pdf.gz | 4.2 MB | Display | |
Data in XML | 6cdo_validation.xml.gz | 21.2 KB | Display | |
Data in CIF | 6cdo_validation.cif.gz | 31 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cd/6cdo ftp://data.pdbj.org/pub/pdb/validation_reports/cd/6cdo | HTTPS FTP |
-Related structure data
Related structure data | 7459C 7460C 8420C 8421C 8422C 5tkjC 5tkkC 6cdeC 6cdiC 6cdmC 6cdpC 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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Unit cell |
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-Components
#1: Antibody | Mass: 24459.482 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human) | ||
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#2: Antibody | Mass: 24041.828 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human) | ||
#3: Protein/peptide | Mass: 732.868 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Human immunodeficiency virus 1 / References: UniProt: Q2N0S5*PLUS | ||
#4: Chemical | ChemComp-SO4 / #5: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.92 Å3/Da / Density % sol: 68.63 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / Details: 0.1 M NaoAc pH 4.5, 2 M AmSO4 |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Jul 23, 2017 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.1→50 Å / Num. obs: 46197 / % possible obs: 100 % / Redundancy: 13.9 % / Biso Wilson estimate: 38.22 Å2 / Rmerge(I) obs: 0.108 / Rpim(I) all: 0.03 / Rrim(I) all: 0.112 / Χ2: 1.009 / Net I/σ(I): 5.7 / Num. measured all: 641724 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
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Refinement | Resolution: 2.099→41.954 Å / SU ML: 0.2 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 25.55
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 95.1 Å2 / Biso mean: 44.8775 Å2 / Biso min: 26.91 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.099→41.954 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 16
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