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Yorodumi- PDB-6cdi: Cryo-EM structure at 3.6 A resolution of vaccine-elicited antibod... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6cdi | ||||||||||||
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Title | Cryo-EM structure at 3.6 A resolution of vaccine-elicited antibody vFP16.02 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 / vFP16.02 | ||||||||||||
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 / structural molecule activity / virion attachment to host cell / host cell plasma membrane / virion membrane / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Human immunodeficiency virus 1 Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||||||||
Authors | Acharya, P. / Xu, K. / Liu, K. / Carragher, B. / Potter, C.S. / Kwong, P.D. | ||||||||||||
Funding support | United States, 3items
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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
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6cdi.cif.gz | 739.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6cdi.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 6cdi.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cd/6cdi ftp://data.pdbj.org/pub/pdb/validation_reports/cd/6cdi | HTTPS FTP |
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-Related structure data
Related structure data | 7460MC 7459C 8420C 8421C 8422C 5tkjC 5tkkC 6cdeC 6cdmC 6cdoC 6cdpC 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
-Glycoprotein ... , 2 types, 6 molecules cADd2C
#1: 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 #2: 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: Human immunodeficiency virus 1 / References: UniProt: Q2N0S5 |
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-Protein , 1 types, 3 molecules q8Q
#6: Protein | Mass: 24653.771 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 , 5 types, 15 molecules n6Nm5Mr7Rh3Hl4L
#3: 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) #4: Antibody | 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) #5: 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) #7: Antibody | Mass: 22455.230 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: 23752.521 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 , 9 types, 57 molecules
#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 | 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 #11: 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 #12: 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 #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: Sugar | ChemComp-NAG / |
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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 |
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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 |
-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 / Calibrated magnification: 22500 X / Nominal defocus max: 4000 nm / Nominal defocus min: 1000 nm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 67.18 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 1893 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 206112 | ||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 57278 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | B value: 106 / Protocol: FLEXIBLE FIT / Space: REAL / Target criteria: Correlation Coefficient |