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- EMDB-26005: Structure of the Inmazeb cocktail and resistance to escape agains... -
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Open data
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Basic information
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Title | Structure of the Inmazeb cocktail and resistance to escape against Ebola virus | ||||||||||||
![]() | Inmazeb cocktail | ||||||||||||
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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 | ![]() ![]() ![]() ![]() | ||||||||||||
Method | 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 SL / Parekh D ...Rayaprolu V / Fulton B / Rafique A / Arturo E / Williams D / Hariharan C / Callaway H / Parvate A / Schendel SL / Parekh D / Hui S / Shaffer K / Pascal KE / Wloga E / Giordano S / Copin R / Franklin M / Boytz RM / Donahue C / Davey R / Baum A / Kyratsous CA / Saphire EO | ||||||||||||
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. | ||||||||||||
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 257.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 27.5 KB 27.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 19.3 KB | Display | ![]() |
Images | ![]() | 27.7 KB | ||
Others | ![]() ![]() | 475.8 MB 475.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 877.4 KB | Display | ![]() |
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Full document | ![]() | 877 KB | Display | |
Data in XML | ![]() | 26.6 KB | Display | |
Data in CIF | ![]() | 35 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7tn9MC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Inmazeb cocktail | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.0504 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Inmazeb cocktail
File | emd_26005_half_map_1.map | ||||||||||||
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Annotation | Inmazeb cocktail | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Inmazeb cocktail
File | emd_26005_half_map_2.map | ||||||||||||
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Annotation | Inmazeb cocktail | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
+Entire : Inmazeb therapeutic cocktail
+Supramolecule #1: Inmazeb therapeutic cocktail
+Supramolecule #2: Envelope glycoprotein, Shed GP
+Supramolecule #3: REGN3471 heavy chain, REGN3479 light chain, REGN3471 light chain,...
+Macromolecule #1: REGN3471 heavy chain
+Macromolecule #2: Envelope glycoprotein
+Macromolecule #3: REGN3479 light chain
+Macromolecule #4: REGN3471 light chain
+Macromolecule #5: GP2
+Macromolecule #6: REGN3479 heavy chain
+Macromolecule #7: REGN3470 heavy chain
+Macromolecule #8: REGN3470 light chain
+Macromolecule #10: 2-acetamido-2-deoxy-beta-D-glucopyranose
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.8 mg/mL | |||||||||
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Buffer | pH: 7.4 Component:
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Grid | Model: C-flat-2/1 / Material: COPPER / Mesh: 200 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 15 sec. | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 4 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Dimensions - Width: 3838 pixel / Digitization - Dimensions - Height: 3710 pixel / Number grids imaged: 3 / Number real images: 6360 / Average exposure time: 6.0 sec. / Average electron dose: 52.4 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Cs: 2.7 mm / Nominal defocus max: 2.6 µm / Nominal defocus min: 0.8 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |