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- PDB-6mph: Cryo-EM structure at 3.8 A resolution of HIV-1 fusion peptide-dir... -
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Basic information
Entry | Database: PDB / ID: 6mph | |||||||||
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Title | Cryo-EM structure at 3.8 A resolution of HIV-1 fusion peptide-directed antibody, DF1W-a.01, elicited by vaccination of Rhesus macaques, in complex with stabilized HIV-1 Env BG505 DS-SOSIP, which was also bound to antibodies VRC03 and PGT122 | |||||||||
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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 / ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Acharya, P. / Xu, K. / Kwong, P.D. | |||||||||
![]() | ![]() Title: Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization. Authors: Rui Kong / Hongying Duan / Zizhang Sheng / Kai Xu / Priyamvada Acharya / Xuejun Chen / Cheng Cheng / Adam S Dingens / Jason Gorman / Mallika Sastry / Chen-Hsiang Shen / Baoshan Zhang / ...Authors: Rui Kong / Hongying Duan / Zizhang Sheng / Kai Xu / Priyamvada Acharya / Xuejun Chen / Cheng Cheng / Adam S Dingens / Jason Gorman / Mallika Sastry / Chen-Hsiang Shen / Baoshan Zhang / Tongqing Zhou / Gwo-Yu Chuang / Cara W Chao / Ying Gu / Alexander J Jafari / Mark K Louder / Sijy O'Dell / Ariana P Rowshan / Elise G Viox / Yiran Wang / Chang W Choi / Martin M Corcoran / Angela R Corrigan / Venkata P Dandey / Edward T Eng / Hui Geng / Kathryn E Foulds / Yicheng Guo / Young D Kwon / Bob Lin / Kevin Liu / Rosemarie D Mason / Martha C Nason / Tiffany Y Ohr / Li Ou / Reda Rawi / Edward K Sarfo / Arne Schön / John P Todd / Shuishu Wang / Hui Wei / Winston Wu / / James C Mullikin / Robert T Bailer / Nicole A Doria-Rose / Gunilla B Karlsson Hedestam / Diana G Scorpio / Julie Overbaugh / Jesse D Bloom / Bridget Carragher / Clinton S Potter / Lawrence Shapiro / Peter D Kwong / John R Mascola / ![]() ![]() Abstract: The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be ...The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization. | |||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 701.9 KB | Display | ![]() |
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PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 9189MC ![]() 8977C ![]() 9319C ![]() 9320C ![]() 9359C ![]() 6mpgC ![]() 6mqcC ![]() 6mqeC ![]() 6mqmC ![]() 6mqrC ![]() 6mqsC ![]() 6n16C ![]() 6n1vC ![]() 6n1wC ![]() 6nf2C ![]() 6osyC ![]() 6ot1C 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
-Envelope glycoprotein ... , 2 types, 6 molecules 6DEABC
#3: Protein | Mass: 17162.525 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() #4: Protein | ![]() Mass: 52986.969 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() |
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-Protein , 2 types, 6 molecules MXYQfg
#5: Protein | Mass: 14838.731 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #7: Protein | Mass: 24653.771 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Antibody , 4 types, 12 molecules 13H24LNZaRhi
#1: Antibody | Mass: 12956.615 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() #2: Antibody | Mass: 12194.694 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() #6: Antibody | Mass: 11591.728 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #8: Antibody | Mass: 11386.774 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Sugars , 6 types, 51 molecules ![](data/chem/img/NAG.gif)
#9: 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 #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 | 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 #12: 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 #13: Polysaccharide | ![]() Source method: isolated from a genetically manipulated source #14: Sugar | ChemComp-NAG / ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
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Molecular weight | Value: 0.63 MDa / Experimental value: YES | ||||||||||||||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||||||||||||||
Specimen | Conc.: 0.25 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||
Specimen support | Details: unspecified | ||||||||||||||||||||||||||||||||||||||||||
Vitrification![]() | Instrument: SPOTITON / 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![]() |
Image recording | Electron dose: 1.78 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.14_3260: / Classification: refinement | |||||||||||||||||||||
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EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||
Symmetry | Point symmetry![]() ![]() | |||||||||||||||||||||
3D reconstruction![]() | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 120981 / Symmetry type: POINT | |||||||||||||||||||||
Refinement | Highest resolution: 3.8 Å |