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- PDB-7tn9: Structure of the Inmazeb cocktail and resistance to escape agains... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7tn9 | ||||||||||||
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Title | Structure of the Inmazeb cocktail and resistance to escape against Ebola virus | ||||||||||||
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![]() | IMMUNE SYSTEM/VIRAL PROTEIN / Ebola / antiviral / therapeutics / IMMUNE SYSTEM-VIRAL PROTEIN complex | ||||||||||||
Function / homology | ![]() host cell endoplasmic reticulum / viral budding from plasma membrane / clathrin-dependent endocytosis of virus by host cell / suppression by virus of host tetherin activity / host cell cytoplasm / entry receptor-mediated virion attachment to host cell / symbiont-mediated suppression of host innate immune response / symbiont entry into host cell / membrane raft / fusion of virus membrane with host endosome membrane ...host cell endoplasmic reticulum / viral budding from plasma membrane / clathrin-dependent endocytosis of virus by host cell / suppression by virus of host tetherin activity / host cell cytoplasm / entry receptor-mediated virion attachment to host cell / symbiont-mediated suppression of host innate immune response / symbiont entry into host cell / membrane raft / fusion of virus membrane with host endosome membrane / lipid binding / viral envelope / host cell plasma membrane / virion membrane / extracellular region / identical protein binding Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() ![]() ![]() Zaire 1976 | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||||||||
![]() | Rayaprolu, V. / Fulton, B. / Rafique, A. / Arturo, E. / Williams, D. / Hariharan, C. / Callaway, H. / Parvate, A. / Schendel, S.L. / Parekh, D. ...Rayaprolu, V. / Fulton, B. / Rafique, A. / Arturo, E. / Williams, D. / Hariharan, C. / Callaway, H. / Parvate, A. / Schendel, S.L. / Parekh, D. / Hui, S. / Shaffer, K. / Pascal, K.E. / Wloga, E. / Giordano, S. / Copin, R. / Franklin, M. / Boytz, R.M. / Donahue, C. / Davey, R. / Baum, A. / Kyratsous, C.A. / Saphire, E.O. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure of the Inmazeb cocktail and resistance to Ebola virus escape. Authors: Vamseedhar Rayaprolu / Benjamin O Fulton / Ashique Rafique / Emilia Arturo / Dewight Williams / Chitra Hariharan / Heather Callaway / Amar Parvate / Sharon L Schendel / Diptiben Parekh / ...Authors: Vamseedhar Rayaprolu / Benjamin O Fulton / Ashique Rafique / Emilia Arturo / Dewight Williams / Chitra Hariharan / Heather Callaway / Amar Parvate / Sharon L Schendel / Diptiben Parekh / Sean Hui / Kelly Shaffer / Kristen E Pascal / Elzbieta Wloga / Stephanie Giordano / Nicole Negron / Min Ni / Richard Copin / Gurinder S Atwal / Matthew Franklin / Ruth Mabel Boytz / Callie Donahue / Robert Davey / Alina Baum / Christos A Kyratsous / Erica Ollmann Saphire / ![]() Abstract: Monoclonal antibodies can provide important pre- or post-exposure protection against infectious disease for those not yet vaccinated or in individuals that fail to mount a protective immune response ...Monoclonal antibodies can provide important pre- or post-exposure protection against infectious disease for those not yet vaccinated or in individuals that fail to mount a protective immune response after vaccination. Inmazeb (REGN-EB3), a three-antibody cocktail against Ebola virus, lessened disease and improved survival in a controlled trial. Here, we present the cryo-EM structure at 3.1 Å of the Ebola virus glycoprotein, determined without symmetry averaging, in a simultaneous complex with the antibodies in the Inmazeb cocktail. This structure allows the modeling of previously disordered portions of the glycoprotein glycan cap, maps the non-overlapping epitopes of Inmazeb, and illuminates the basis for complementary activities and residues critical for resistance to escape by these and other clinically relevant antibodies. We further provide direct evidence that Inmazeb protects against the rapid emergence of escape mutants, whereas monotherapies even against conserved epitopes do not, supporting the benefit of a cocktail versus a monotherapy approach. | ||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 526.1 KB | Display | ![]() |
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PDB format | ![]() | 420.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.8 MB | Display | ![]() |
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Full document | ![]() | 1.8 MB | Display | |
Data in XML | ![]() | 102 KB | Display | |
Data in CIF | ![]() | 154.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 26005MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 2 types, 6 molecules TSUWVX
#2: Protein | Mass: 35605.875 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #5: Protein | Mass: 15795.782 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Antibody , 6 types, 16 molecules ACERNPFBDQMOGIHJ
#1: Antibody | Mass: 23020.711 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #3: Antibody | Mass: 23228.734 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #4: Antibody | Mass: 24172.803 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #6: Antibody | Mass: 22856.572 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #7: Antibody | Mass: 23187.951 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #8: Antibody | Mass: 23474.076 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
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-Sugars , 2 types, 11 molecules ![](data/chem/img/NAG.gif)
#9: Polysaccharide | Source method: isolated from a genetically manipulated source #10: Sugar | ChemComp-NAG / |
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-Details
Has ligand of interest | Y |
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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 |
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Sample preparation
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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 | ||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.8 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: C-flat-2/1 | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 4 K |
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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: ![]() |
Electron lens | Mode: OTHER / Nominal defocus max: 2600 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 6 sec. / Electron dose: 52.4 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 3 / Num. of real images: 6360 |
Image scans | Width: 3838 / Height: 3710 / Movie frames/image: 30 |
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Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 3154 | ||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 276715 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 5JQ3 | ||||||||||||||||||||||||||||
Refine LS restraints |
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