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Yorodumi- PDB-6dzm: Bundibugyo virus GP (mucin-deleted) in complex with pan-ebolaviru... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6dzm | |||||||||
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Title | Bundibugyo virus GP (mucin-deleted) in complex with pan-ebolavirus human antibody ADI-15878 Fab | |||||||||
Components |
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Keywords | VIRAL PROTEIN / antibody / pan-ebolavirus / internal fusion loop / HR1 / glycoprotein | |||||||||
Function / homology | Filoviruses glycoprotein, extracellular domain / Filoviruses glycoprotein / Filovirus glycoprotein / viral envelope / extracellular region / membrane / Envelope glycoprotein Function and homology information | |||||||||
Biological species | Bundibugyo ebolavirus Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.29 Å | |||||||||
Authors | Murin, C.D. / Ward, A.B. | |||||||||
Funding support | United States, 1items
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Citation | Journal: Cell Rep / Year: 2018 Title: Structural Basis of Pan-Ebolavirus Neutralization by an Antibody Targeting the Glycoprotein Fusion Loop. Authors: Charles D Murin / Jessica F Bruhn / Zachary A Bornholdt / Jeffrey Copps / Robyn Stanfield / Andrew B Ward / Abstract: Monoclonal antibodies (mAbs) with pan-ebolavirus cross-reactivity are highly desirable, but development of such mAbs is limited by a lack of a molecular understanding of cross-reactive epitopes. The ...Monoclonal antibodies (mAbs) with pan-ebolavirus cross-reactivity are highly desirable, but development of such mAbs is limited by a lack of a molecular understanding of cross-reactive epitopes. The antibody ADI-15878 was previously identified from a human survivor of Ebola virus Makona variant (EBOV/Mak) infection. This mAb demonstrated potent neutralizing activity against all known ebolaviruses and provided protection in rodent and ferret models against three ebolavirus species. Here, we describe the unliganded crystal structure of ADI-15878 as well as the cryo-EM structures of ADI-15878 in complex with the EBOV/Mak and Bundibugyo virus (BDBV) glycoproteins (GPs). ADI-15878 binds through an induced-fit mechanism by targeting highly conserved residues in the internal fusion loop (IFL), bridging across GP protomers via the heptad repeat 1 (HR1) region. Our structures provide a more complete description of the ebolavirus immunogenic landscape, as well as a molecular basis for how rare but potent antibodies target conserved filoviral fusion machinery. | |||||||||
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 | 6dzm.cif.gz | 306.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6dzm.ent.gz | 251.2 KB | Display | PDB format |
PDBx/mmJSON format | 6dzm.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dz/6dzm ftp://data.pdbj.org/pub/pdb/validation_reports/dz/6dzm | HTTPS FTP |
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-Related structure data
Related structure data | 8936MC 8935C 6dzlC 6dznC 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
-Bundibugyo virus ... , 2 types, 6 molecules ABCDEF
#1: Protein | Mass: 34697.938 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bundibugyo ebolavirus / Gene: GP, DF49_53413gpGP, DH33_45404gpGP / Cell line (production host): HEK 293F / Production host: Homo sapiens (human) / References: UniProt: B8XCN0 #2: Protein | Mass: 19683.902 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bundibugyo ebolavirus / Gene: GP, DF49_53413gpGP, DH33_45404gpGP / Cell line (production host): HEK 293F / Production host: Homo sapiens (human) / References: UniProt: B8XCN0 |
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-Antibody , 2 types, 6 molecules HKLGIJ
#3: Antibody | Mass: 11333.459 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Nicotiana benthamiana (plant) #4: Antibody | Mass: 13043.574 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Nicotiana benthamiana (plant) |
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-Sugars , 3 types, 12 molecules
#5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: Sugar | ChemComp-NAG / |
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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
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Molecular weight |
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 Details: Solutions were made fresh from 10X concentrate and filtered with a 0.2 micrometer filter into a sterile glass container. | ||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Antibody ADI-15878 Fab was added in 10 molar excess to glycoprotein and allowed to incubate overnight at 4 degrees Celsius followed by size exclusion chromatography to purify the complex and rid of excess Fab. | ||||||||||||||||||||||||||||
Specimen support | Details: unspecified | ||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K Details: 3.5s blot on both sides of the grid using Whattman No. 1 filter paper |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS / Details: Preliminary grid screening was performed manually |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Calibrated magnification: 38167 X / Nominal defocus max: 3500 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 60 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement | ||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.29 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 35961 / Symmetry type: POINT |