+Open data
-Basic information
Entry | Database: PDB / ID: 6vo3 | |||||||||||||||
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Title | AMC009 SOSIP.v4.2 in complex with PGV04 Fab | |||||||||||||||
Components |
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Keywords | IMMUNE SYSTEM / HIV / Env / antibody / VIRAL PROTEIN | |||||||||||||||
Biological species | Homo sapiens (human) Human immunodeficiency virus 1 | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.25 Å | |||||||||||||||
Authors | Cottrell, C.A. / de Val, N. / Ward, A.B. | |||||||||||||||
Funding support | United States, 4items
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Citation | Journal: J Virol / Year: 2020 Title: Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers. Authors: Anna Schorcht / Tom L G M van den Kerkhof / Christopher A Cottrell / Joel D Allen / Jonathan L Torres / Anna-Janina Behrens / Edith E Schermer / Judith A Burger / Steven W de Taeye / Alba ...Authors: Anna Schorcht / Tom L G M van den Kerkhof / Christopher A Cottrell / Joel D Allen / Jonathan L Torres / Anna-Janina Behrens / Edith E Schermer / Judith A Burger / Steven W de Taeye / Alba Torrents de la Peña / Ilja Bontjer / Stephanie Gumbs / Gabriel Ozorowski / Celia C LaBranche / Natalia de Val / Anila Yasmeen / Per Johan Klasse / David C Montefiori / John P Moore / Hanneke Schuitemaker / Max Crispin / Marit J van Gils / Andrew B Ward / Rogier W Sanders / Abstract: The induction of broadly neutralizing antibodies (bNAbs) is a major goal in vaccine research. HIV-1-infected individuals that develop exceptionally strong bNAb responses, termed elite neutralizers, ...The induction of broadly neutralizing antibodies (bNAbs) is a major goal in vaccine research. HIV-1-infected individuals that develop exceptionally strong bNAb responses, termed elite neutralizers, can inform vaccine design by providing blueprints for the induction of similar bNAb responses. We describe a new recombinant native-like envelope glycoprotein (Env) SOSIP trimer, termed AMC009, based on the viral founder sequences of an elite neutralizer. The subtype B AMC009 SOSIP protein formed stable native-like trimers that displayed multiple bNAb epitopes. Overall, its structure at 4.3-Å resolution was similar to that of BG505 SOSIP.664. The AMC009 trimer resembled one from a second elite neutralizer, AMC011, in having a dense and complete glycan shield. When tested as immunogens in rabbits, the AMC009 trimers did not induce autologous neutralizing antibody (NAb) responses efficiently while the AMC011 trimers did so very weakly, outcomes that may reflect the completeness of their glycan shields. The AMC011 trimer induced antibodies that occasionally cross-neutralized heterologous tier 2 viruses, sometimes at high titer. Cross-neutralizing antibodies were more frequently elicited by a trivalent combination of AMC008, AMC009, and AMC011 trimers, all derived from subtype B viruses. Each of these three individual trimers could deplete the NAb activity from the rabbit sera. Mapping the polyclonal sera by electron microscopy revealed that antibodies of multiple specificities could bind to sites on both autologous and heterologous trimers. These results advance our understanding of how to use Env trimers in multivalent vaccination regimens and the immunogenicity of trimers derived from elite neutralizers. Elite neutralizers, i.e., individuals who developed unusually broad and potent neutralizing antibody responses, might serve as blueprints for HIV-1 vaccine design. Here, we studied the immunogenicity of native-like recombinant envelope glycoprotein (Env) trimers based on viral sequences from elite neutralizers. While immunization with single trimers from elite neutralization did not recapitulate the breadth and potency of neutralization observed in these infected individuals, a combination of three subtype B Env trimers from elite neutralizers resulted in some neutralization breadth within subtype B viruses. These results should guide future efforts to design vaccines to induce 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 | 6vo3.cif.gz | 498.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6vo3.ent.gz | 412.2 KB | Display | PDB format |
PDBx/mmJSON format | 6vo3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6vo3_validation.pdf.gz | 2.1 MB | Display | wwPDB validaton report |
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Full document | 6vo3_full_validation.pdf.gz | 2.1 MB | Display | |
Data in XML | 6vo3_validation.xml.gz | 71.8 KB | Display | |
Data in CIF | 6vo3_validation.cif.gz | 109.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vo/6vo3 ftp://data.pdbj.org/pub/pdb/validation_reports/vo/6vo3 | HTTPS FTP |
-Related structure data
Related structure data | 21258MC 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
-AMC009 SOSIP.v4.2 envelope glycoprotein ... , 2 types, 6 molecules ACDBEF
#3: Protein | Mass: 54113.422 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Cell line (production host): HEK293F / Production host: Homo sapiens (human) #4: Protein | Mass: 17391.799 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: env / Cell line (production host): HEK293F / Production host: Homo sapiens (human) |
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-Antibody / Protein , 2 types, 6 molecules HGILJK
#1: Antibody | Mass: 24644.771 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293F / Production host: Homo sapiens (human) #2: Protein | Mass: 23073.822 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293F / Production host: Homo sapiens (human) |
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-Sugars , 4 types, 39 molecules
#5: 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 #6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: 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 #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 | Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Details: unspecified | ||||||||||||||||||||||||
Vitrification | Instrument: HOMEMADE PLUNGER / 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 FIELD / Cs: 2.7 mm |
Specimen holder | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 7 sec. / Electron dose: 32 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 3021 |
Image scans | Movie frames/image: 35 |
-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: 4.25 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 128752 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL |