+Open data
-Basic information
Entry | Database: PDB / ID: 7kej | |||||||||
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Title | BDBV-289 bound to EBOV GPdMuc Makona | |||||||||
Components |
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Keywords | VIRAL PROTEIN/Immune System / ebolavirus / glycan cap / antibody / broadly neutralizing / filovirus / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex | |||||||||
Function / homology | Envelope glycoprotein GP2-like, HR1-HR2 / Filoviruses glycoprotein, extracellular domain / Filoviruses glycoprotein / Filovirus glycoprotein / extracellular region / membrane / Virion spike glycoprotein / Virion spike glycoprotein Function and homology information | |||||||||
Biological species | Ebola virus Homo sapiens (human) Zaire ebolavirus | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
Authors | Murin, C.D. / Ward, A.B. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Cell Rep / Year: 2021 Title: Convergence of a common solution for broad ebolavirus neutralization by glycan cap-directed human antibodies. Authors: Charles D Murin / Pavlo Gilchuk / Philipp A Ilinykh / Kai Huang / Natalia Kuzmina / Xiaoli Shen / Jessica F Bruhn / Aubrey L Bryan / Edgar Davidson / Benjamin J Doranz / Lauren E Williamson ...Authors: Charles D Murin / Pavlo Gilchuk / Philipp A Ilinykh / Kai Huang / Natalia Kuzmina / Xiaoli Shen / Jessica F Bruhn / Aubrey L Bryan / Edgar Davidson / Benjamin J Doranz / Lauren E Williamson / Jeffrey Copps / Tanwee Alkutkar / Andrew I Flyak / Alexander Bukreyev / James E Crowe / Andrew B Ward / Abstract: Antibodies that target the glycan cap epitope on the ebolavirus glycoprotein (GP) are common in the adaptive response of survivors. A subset is known to be broadly neutralizing, but the details of ...Antibodies that target the glycan cap epitope on the ebolavirus glycoprotein (GP) are common in the adaptive response of survivors. A subset is known to be broadly neutralizing, but the details of their epitopes and basis for neutralization are not well understood. Here, we present cryoelectron microscopy (cryo-EM) structures of diverse glycan cap antibodies that variably synergize with GP base-binding antibodies. These structures describe a conserved site of vulnerability that anchors the mucin-like domains (MLDs) to the glycan cap, which we call the MLD anchor and cradle. Antibodies that bind to the MLD cradle share common features, including use of IGHV1-69 and IGHJ6 germline genes, which exploit hydrophobic residues and form β-hairpin structures to mimic the MLD anchor, disrupt MLD attachment, destabilize GP quaternary structure, and block cleavage events required for receptor binding. Our results provide a molecular basis for ebolavirus neutralization by broadly reactive glycan cap 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 | 7kej.cif.gz | 368.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7kej.ent.gz | 293.8 KB | Display | PDB format |
PDBx/mmJSON format | 7kej.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7kej_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 7kej_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 7kej_validation.xml.gz | 55.9 KB | Display | |
Data in CIF | 7kej_validation.cif.gz | 84.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ke/7kej ftp://data.pdbj.org/pub/pdb/validation_reports/ke/7kej | HTTPS FTP |
-Related structure data
Related structure data | 22839MC 7kewC 7kexC 7kf9C 7kfbC 7kfeC 7kfgC 7kfhC 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
-Virion spike ... , 2 types, 6 molecules BCAEFD
#1: Protein | Mass: 34978.613 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Ebola virus / Gene: GP / Cell line (production host): HEK 293F / Production host: Homo sapiens (human) / References: UniProt: A0A1C4HDV6 #4: Protein | Mass: 22158.592 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Zaire ebolavirus / Gene: GP / Cell line (production host): HEK 293F / Production host: Homo sapiens (human) / References: UniProt: A0A0E3XK95 |
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-Antibody , 2 types, 6 molecules HIGKLJ
#2: Antibody | Mass: 26864.316 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK 293F / Production host: Homo sapiens (human) #3: Antibody | Mass: 24725.422 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK 293F / Production host: Homo sapiens (human) |
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-Sugars , 2 types, 12 molecules
#5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: 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 | Name: Complex of Ebola virus GP (mucin-deleted Makona strain) bound to BDBV-289 Fab Type: COMPLEX Details: Fab and GP expressed in HEK 293F cells, complexed and purified by size exclusion chromatography Entity ID: #1-#4 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: HEK 293F / Plasmid: pPPI4 and AbVec |
Details of virus | Isolate: STRAIN / Type: VIRION |
Buffer solution | pH: 7.4 |
Specimen | 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 FIELD |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 32108 / Symmetry type: POINT |