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- PDB-8euw: Cryo-EM structure of HIV-1 BG505 DS-SOSIP ENV trimer bound to VRC... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8euw | ||||||
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Title | Cryo-EM structure of HIV-1 BG505 DS-SOSIP ENV trimer bound to VRC34.01-MM28 FAB | ||||||
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / broadly neutralizing antibody / fusion peptide / HIV-1 / glycoprotein / viral protein / FP-targeting vaccines / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
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 / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å | ||||||
![]() | Pletnev, S. / Kwong, P. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Antibody-directed evolution reveals a mechanism for enhanced neutralization at the HIV-1 fusion peptide site. Authors: Bailey B Banach / Sergei Pletnev / Adam S Olia / Kai Xu / Baoshan Zhang / Reda Rawi / Tatsiana Bylund / Nicole A Doria-Rose / Thuy Duong Nguyen / Ahmed S Fahad / Myungjin Lee / Bob C Lin / ...Authors: Bailey B Banach / Sergei Pletnev / Adam S Olia / Kai Xu / Baoshan Zhang / Reda Rawi / Tatsiana Bylund / Nicole A Doria-Rose / Thuy Duong Nguyen / Ahmed S Fahad / Myungjin Lee / Bob C Lin / Tracy Liu / Mark K Louder / Bharat Madan / Krisha McKee / Sijy O'Dell / Mallika Sastry / Arne Schön / Natalie Bui / Chen-Hsiang Shen / Jacy R Wolfe / Gwo-Yu Chuang / John R Mascola / Peter D Kwong / Brandon J DeKosky / ![]() Abstract: The HIV-1 fusion peptide (FP) represents a promising vaccine target, but global FP sequence diversity among circulating strains has limited anti-FP antibodies to ~60% neutralization breadth. Here we ...The HIV-1 fusion peptide (FP) represents a promising vaccine target, but global FP sequence diversity among circulating strains has limited anti-FP antibodies to ~60% neutralization breadth. Here we evolve the FP-targeting antibody VRC34.01 in vitro to enhance FP-neutralization using site saturation mutagenesis and yeast display. Successive rounds of directed evolution by iterative selection of antibodies for binding to resistant HIV-1 strains establish a variant, VRC34.01_mm28, as a best-in-class antibody with 10-fold enhanced potency compared to the template antibody and ~80% breadth on a cross-clade 208-strain neutralization panel. Structural analyses demonstrate that the improved paratope expands the FP binding groove to accommodate diverse FP sequences of different lengths while also recognizing the HIV-1 Env backbone. These data reveal critical antibody features for enhanced neutralization breadth and potency against the FP site of vulnerability and accelerate clinical development of broad HIV-1 FP-targeting vaccines and therapeutics. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 499 KB | Display | ![]() |
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PDB format | ![]() | 408.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 28619MC ![]() 8eliC ![]() 8euuC ![]() 8euvC ![]() 8f7zC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Envelope glycoprotein ... , 2 types, 6 molecules ACEBDF
#1: Protein | Mass: 54086.324 Da / Num. of mol.: 3 / Fragment: UNP residues 30-510 Source method: isolated from a genetically manipulated source Details: BG505 DS-SOSIP GP120 / Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 17146.482 Da / Num. of mol.: 3 / Fragment: UNP residues 509-661 Source method: isolated from a genetically manipulated source Details: BG505 DS-SOSIP GP41 / Source: (gene. exp.) ![]() ![]() ![]() |
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-Antibody , 2 types, 6 molecules GIKHJL
#3: Antibody | Mass: 23869.789 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #4: Antibody | Mass: 23138.766 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Sugars , 4 types, 45 molecules ![](data/chem/img/NAG.gif)
#5: 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 #6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: Polysaccharide | Source method: isolated from a genetically manipulated source #8: Sugar | ChemComp-NAG / |
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-Non-polymers , 1 types, 180 molecules ![](data/chem/img/HOH.gif)
#9: Water | ChemComp-HOH / |
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-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 |
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Sample preparation
Component | Name: BG505 DS-SOSIP VRC34.01-MM28 FAB COMPLEX / Type: COMPLEX / Entity ID: #1-#4 / Source: MULTIPLE SOURCES | ||||||||||||
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Source (natural) |
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Source (recombinant) | Organism: ![]() | ||||||||||||
Details of virus | Empty: YES / Enveloped: YES / Isolate: OTHER / Type: VIRUS-LIKE PARTICLE | ||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R2/2 | ||||||||||||
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 / Nominal defocus max: 2000 nm / Nominal defocus min: 700 nm / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 43.5 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of real images: 9616 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 3780744 | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 918637 / Num. of class averages: 40 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL |