+Open data
-Basic information
Entry | Database: PDB / ID: 7m8l | |||||||||
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Title | EBOV GP bound to rEBOV-442 and rEBOV-515 Fabs | |||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / ebolavirus / EBOV / antibody / antibody therapeutic / mAbs / 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) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Murin, C.D. / Ward, A.B. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Cell / Year: 2021 Title: Pan-ebolavirus protective therapy by two multifunctional human antibodies. Authors: Pavlo Gilchuk / Charles D Murin / Robert W Cross / Philipp A Ilinykh / Kai Huang / Natalia Kuzmina / Viktoriya Borisevich / Krystle N Agans / Joan B Geisbert / Seth J Zost / Rachel S Nargi / ...Authors: Pavlo Gilchuk / Charles D Murin / Robert W Cross / Philipp A Ilinykh / Kai Huang / Natalia Kuzmina / Viktoriya Borisevich / Krystle N Agans / Joan B Geisbert / Seth J Zost / Rachel S Nargi / Rachel E Sutton / Naveenchandra Suryadevara / Robin G Bombardi / Robert H Carnahan / Alexander Bukreyev / Thomas W Geisbert / Andrew B Ward / James E Crowe / Abstract: Ebolaviruses cause a severe and often fatal illness with the potential for global spread. Monoclonal antibody-based treatments that have become available recently have a narrow therapeutic spectrum ...Ebolaviruses cause a severe and often fatal illness with the potential for global spread. Monoclonal antibody-based treatments that have become available recently have a narrow therapeutic spectrum and are ineffective against ebolaviruses other than Ebola virus (EBOV), including medically important Bundibugyo (BDBV) and Sudan (SUDV) viruses. Here, we report the development of a therapeutic cocktail comprising two broadly neutralizing human antibodies, rEBOV-515 and rEBOV-442, that recognize non-overlapping sites on the ebolavirus glycoprotein (GP). Antibodies in the cocktail exhibited synergistic neutralizing activity, resisted viral escape, and possessed differing requirements for their Fc-regions for optimal in vivo activities. The cocktail protected non-human primates from ebolavirus disease caused by EBOV, BDBV, or SUDV with high therapeutic effectiveness. High-resolution structures of the cocktail antibodies in complex with GP revealed the molecular determinants for neutralization breadth and potency. This study provides advanced preclinical data to support clinical development of this cocktail for pan-ebolavirus therapy. | |||||||||
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 | 7m8l.cif.gz | 497.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7m8l.ent.gz | 401.4 KB | Display | PDB format |
PDBx/mmJSON format | 7m8l.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7m8l_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 7m8l_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 7m8l_validation.xml.gz | 71.8 KB | Display | |
Data in CIF | 7m8l_validation.cif.gz | 110.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/m8/7m8l ftp://data.pdbj.org/pub/pdb/validation_reports/m8/7m8l | HTTPS FTP |
-Related structure data
Related structure data | 23719MC 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 glycoprotein ... , 2 types, 6 molecules ABCDEF
#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 / 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.) Ebola virus / Gene: GP / Production host: Homo sapiens (human) / References: UniProt: A0A0E3XK95 |
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-Antibody , 4 types, 12 molecules GHIJKLMNOPQR
#2: Antibody | Mass: 25179.199 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #3: Antibody | Mass: 23715.314 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #5: Antibody | Mass: 24047.846 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #6: Antibody | Mass: 23528.092 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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-Sugars , 3 types, 15 molecules
#7: 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 #8: Polysaccharide | Source method: isolated from a genetically manipulated source #9: 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 mucin deleted Ebola virus GP (Makona variant) bound to rEBOV-442 and rEBOV-515 Fabs Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT | ||||||||||||
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Source (natural) |
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Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||
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: 50 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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Symmetry | Point symmetry: C3 (3 fold cyclic) |
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 21285 / Symmetry type: POINT |