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- PDB-6cde: Cryo-EM structure at 3.8 A resolution of vaccine-elicited antibod... -
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Basic information
Entry | Database: PDB / ID: 6cde | |||||||||
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Title | Cryo-EM structure at 3.8 A resolution of vaccine-elicited antibody vFP20.01 in complex with HIV-1 Env BG505 DS-SOSIP, and antibodies VRC03 and PGT122 | |||||||||
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![]() | VIRAL PROTEIN / HIV-1 Env / BG505 SOSIP / fusion peptide / VRC03 / PGT122 / vFP20.01 | |||||||||
Function / homology | ![]() 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 | ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
![]() | Acharya, P. / Xu, K. / Liu, K. / Carragher, B. / Potter, C.S. / Kwong, P.D. | |||||||||
Funding support | ![]()
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![]() | ![]() 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
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Structure viewer | Molecule: ![]() ![]() |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 7459MC ![]() 7460C ![]() 8420C ![]() 8421C ![]() 8422C ![]() 5tkjC ![]() 5tkkC ![]() 6cdiC ![]() 6cdmC ![]() 6cdoC ![]() 6cdpC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 1 types, 3 molecules Qq5
#6: Protein | Mass: 24653.771 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Glycoprotein ... , 2 types, 6 molecules Dd1Cc2
#7: Protein | Mass: 17162.525 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #8: Protein | Mass: 52986.969 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Antibody , 5 types, 15 molecules hH3lL4Mm7Nn8Rr6
#1: Antibody | Mass: 22673.586 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Antibody | Mass: 23826.666 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #3: Antibody | Mass: 24710.848 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #4: Antibody | Mass: 22560.941 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #5: Antibody | Mass: 23043.652 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Sugars , 11 types, 63 molecules ![](data/chem/img/NAG.gif)
![](data/chem/img/MAN.gif)
![](data/chem/img/MAN.gif)
#9: 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 #10: 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 #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: Polysaccharide | Source method: isolated from a genetically manipulated source #15: Polysaccharide | Source method: isolated from a genetically manipulated source #16: Polysaccharide | Source method: isolated from a genetically manipulated source #17: Polysaccharide | Source method: isolated from a genetically manipulated source #18: Sugar | ChemComp-NAG / #19: Sugar | |
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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 |
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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 | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Calibrated magnification: 130000 X / Calibrated defocus min: -1800 nm / Calibrated defocus max: -2800 nm |
Image recording | Electron dose: 70.7 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 723 |
Image scans | Movie frames/image: 40 / Used frames/image: 1-40 |
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Processing
Software | Name: PHENIX / Version: 1.11.1_2575: / 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: 108962 | ||||||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 48248 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | B value: 107 / Protocol: FLEXIBLE FIT / Space: REAL / Target criteria: Correlation Coefficient | ||||||||||||||||||||||||||||
Refinement | Highest resolution: 3.8 Å | ||||||||||||||||||||||||||||
Refine LS restraints |
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