+
Open data
-
Basic information
Entry | Database: EMDB / ID: EMD-8701 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | EBOV GPdMuc:ADI-15946 | |||||||||
![]() | Complex of recombinant Ebola virus glycoprotein with human IgG1 Fab ADI-15946 from survivor. | |||||||||
![]() |
| |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / negative staining / Resolution: 24.7 Å | |||||||||
![]() | Murin CD / Ward AB / Turner HL | |||||||||
![]() | ![]() Title: Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses. Authors: Anna Z Wec / Andrew S Herbert / Charles D Murin / Elisabeth K Nyakatura / Dafna M Abelson / J Maximilian Fels / Shihua He / Rebekah M James / Marc-Antoine de La Vega / Wenjun Zhu / Russell R ...Authors: Anna Z Wec / Andrew S Herbert / Charles D Murin / Elisabeth K Nyakatura / Dafna M Abelson / J Maximilian Fels / Shihua He / Rebekah M James / Marc-Antoine de La Vega / Wenjun Zhu / Russell R Bakken / Eileen Goodwin / Hannah L Turner / Rohit K Jangra / Larry Zeitlin / Xiangguo Qiu / Jonathan R Lai / Laura M Walker / Andrew B Ward / John M Dye / Kartik Chandran / Zachary A Bornholdt / ![]() ![]() Abstract: Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has ...Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GP) generated in host cell endosomes. Only a few somatic hypermutations are required for broad antiviral activity, and germline-approximating variants display enhanced GP recognition, suggesting that such antibodies could be elicited more efficiently with suitably optimized GP immunogens. Our findings inform the development of both broadly effective immunotherapeutics and vaccines against filoviruses. | |||||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
-
Downloads & links
-EMDB archive
Map data | ![]() | 754.1 KB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 14.5 KB 14.5 KB | Display Display | ![]() |
Images | ![]() | 33.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
-
Links
EMDB pages | ![]() ![]() |
---|
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Complex of recombinant Ebola virus glycoprotein with human IgG1 Fab ADI-15946 from survivor. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 4.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-
Sample components
-Entire : EBOV GPdMuc:ADI-15946
Entire | Name: EBOV GPdMuc:ADI-15946 |
---|---|
Components |
|
-Supramolecule #1: EBOV GPdMuc:ADI-15946
Supramolecule | Name: EBOV GPdMuc:ADI-15946 / type: complex / ID: 1 / Parent: 0 Details: Complex of recombinant Ebola virus glycoprotein and human IgG1 Fab ADI-15946 from a survivor. |
---|---|
Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Supramolecule #2: EBOV GPdMuc
Supramolecule | Name: EBOV GPdMuc / type: complex / ID: 2 / Parent: 1 Details: Recombinant mucin-deleted Ebola virus glycoprotein expressed in mammalian cells, 293F. |
---|---|
Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Supramolecule #3: ADI-15946 Fab
Supramolecule | Name: ADI-15946 Fab / type: complex / ID: 3 / Parent: 1 Details: Fab fragment generated by proteolytic cleavage of IgG antibody, expressed in plant system. |
---|---|
Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Supramolecule #4: ADI-15946 Fab
Supramolecule | Name: ADI-15946 Fab / type: complex / ID: 4 / Parent: 1 Details: Fab fragment generated by proteolytic cleavage of IgG antibody, expressed in plant system. |
---|---|
Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Experimental details
-Structure determination
Method | negative staining |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Concentration | 0.03 mg/mL | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Buffer | pH: 7.4 Component:
Details: Solutions were made from a 10X stock and filtered sterilized. | |||||||||
Staining | Type: NEGATIVE / Material: Uranyl Formate Details: Negatively stained EM specimens were prepared using a side-blotting technique and uranyl-formate stain. | |||||||||
Grid | Model: Protochip / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Atmosphere: OTHER | |||||||||
Details | Monodisperse sample deposited on negative stain grid. |
-
Electron microscopy
Microscope | FEI TECNAI SPIRIT |
---|---|
Image recording | Film or detector model: TVIPS TEMCAM-F416 (4k x 4k) / Number grids imaged: 1 / Number real images: 74 / Average electron dose: 2.0 e/Å2 |
Electron beam | Acceleration voltage: 120 kV / Electron source: LAB6 |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus min: 1.0 µm |
Sample stage | Specimen holder model: SIDE ENTRY, EUCENTRIC |
Experimental equipment | ![]() Model: Tecnai Spirit / Image courtesy: FEI Company |