+Open data
-Basic information
Entry | Database: PDB / ID: 6u59 | ||||||||||||
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Title | HIV-1 B41 SOSIP.664 in complex with rabbit antibody 13B | ||||||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 / rabbit antibody / SOSIP / VIRAL PROTEIN-IMMUNE SYSTEM 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 | Human immunodeficiency virus 1 Oryctolagus cuniculus (rabbit) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.86 Å | ||||||||||||
Authors | Yang, Y.R. / Ward, A.B. | ||||||||||||
Funding support | United States, 3items
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Citation | Journal: J Virol / Year: 2020 Title: Autologous Antibody Responses to an HIV Envelope Glycan Hole Are Not Easily Broadened in Rabbits. Authors: Yuhe R Yang / Laura E McCoy / Marit J van Gils / Raiees Andrabi / Hannah L Turner / Meng Yuan / Christopher A Cottrell / Gabriel Ozorowski / James Voss / Matthias Pauthner / Thomas M ...Authors: Yuhe R Yang / Laura E McCoy / Marit J van Gils / Raiees Andrabi / Hannah L Turner / Meng Yuan / Christopher A Cottrell / Gabriel Ozorowski / James Voss / Matthias Pauthner / Thomas M Polveroni / Terrence Messmer / Ian A Wilson / Rogier W Sanders / Dennis R Burton / Andrew B Ward / Abstract: Extensive studies with subtype A BG505-derived HIV envelope glycoprotein (Env) immunogens have revealed that the dominant autologous neutralizing epitope in rabbits is located in an exposed region of ...Extensive studies with subtype A BG505-derived HIV envelope glycoprotein (Env) immunogens have revealed that the dominant autologous neutralizing epitope in rabbits is located in an exposed region of the heavily glycosylated trimer that lacks potential N-linked glycosylation sites at positions 230, 241, and 289. The Env derived from B41, a subtype B virus, shares a glycan hole centered on positions 230 and 289. To test whether broader neutralization to the common glycan hole can be achieved, we immunized rabbits with B41 SOSIP (gp120-gp41 disulfide [SOS] with an isoleucine-to-proline mutation [IP] in gp41) alone, as well as B41 and BG505 coimmunization. We isolated autologous neutralizing antibodies (nAbs) and described their structure in complex with the B41 Env. Our data suggest that distinct autologous nAb lineages are induced by BG505 and B41 immunogens, even when both were administered together. In contrast to previously described BG505 glycan hole antibodies, the B41-specific nAbs accommodate the >97% conserved N241 glycan, which is present in B41. Single-particle cryo-electron microscopy studies confirmed that B41- and BG505-specific nAbs bind to overlapping glycan hole epitopes. We then used our high-resolution data to guide mutations in the BG505 glycan hole epitope in an attempt to broaden the reactivity of a B41-specific nAb, but we recovered only partial binding. Our data demonstrate that the lack of cross-reactivity in glycan hole antibodies is due to amino acid differences within the epitope, and our attempts to rationally design cross-reactive trimers resulted in only limited success. Thus, even for the immunodominant glycan hole shared between BG505 and B41, the prospect of designing prime-boost immunogens remains difficult. A glycan hole is one of the most dominant autologous neutralizing epitopes targeted on BG505 and B41 SOSIP trimer-immunized rabbits. Our high-resolution cryo-electron microscopy (cryoEM) studies of B41 in complex with a B41-specific antibody complex elucidate the molecular basis of this strain-specific glycan hole response. We conclude that even for the immunodominant glycan hole shared between BG505 and B41, the prospect of designing prime-boost immunogens remains difficult. | ||||||||||||
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 | 6u59.cif.gz | 510.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6u59.ent.gz | 422.1 KB | Display | PDB format |
PDBx/mmJSON format | 6u59.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6u59_validation.pdf.gz | 2.7 MB | Display | wwPDB validaton report |
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Full document | 6u59_full_validation.pdf.gz | 2.7 MB | Display | |
Data in XML | 6u59_validation.xml.gz | 56 KB | Display | |
Data in CIF | 6u59_validation.cif.gz | 93 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/u5/6u59 ftp://data.pdbj.org/pub/pdb/validation_reports/u5/6u59 | HTTPS FTP |
-Related structure data
Related structure data | 20642MC 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
-Protein , 2 types, 6 molecules ACGBDI
#1: Protein | Mass: 58872.902 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Strain: B41 / Cell line (production host): HEK 293F / Production host: Homo sapiens (human) / References: UniProt: B3UES2 #2: Protein | Mass: 17357.824 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Strain: B41 / Cell line (production host): HEK 293F / Production host: Homo sapiens (human) / References: UniProt: B3UEZ6 |
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-Antibody , 2 types, 6 molecules LEJHFK
#3: Antibody | Mass: 11977.202 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Oryctolagus cuniculus (rabbit) / Cell line (production host): HEK 293F / Production host: Homo sapiens (human) #4: Antibody | Mass: 12790.192 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Oryctolagus cuniculus (rabbit) / Cell line (production host): HEK 293F / Production host: Homo sapiens (human) |
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-Sugars , 4 types, 69 molecules
#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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-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 |
-Sample preparation
Component |
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Molecular weight | Value: 0.57 MDa / Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 Details: Detergent was added to sample shortly prior to freezing. | ||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: C-flat-2/2 | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 36000 X / Nominal defocus max: 2000 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm / C2 aperture diameter: 70 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 14 sec. / Electron dose: 60 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 1721 |
Image scans | Sampling size: 5 µm / Movie frames/image: 56 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.86 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 147520 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL |