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- EMDB-16173: Alpha7-nAChR extracellular ligand-binding domain (alpha7-ECD)in c... -
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Open data
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Basic information
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Title | Alpha7-nAChR extracellular ligand-binding domain (alpha7-ECD)in complex with a weak neurotoxin WTX. | |||||||||
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Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.6 Å | |||||||||
![]() | Chesnokov YM / Kamyshinsky RA | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Membrane-mediated interaction of non-conventional snake three-finger toxins with nicotinic acetylcholine receptors. Authors: Zakhar O Shenkarev / Yuri M Chesnokov / Maxim M Zaigraev / Anton O Chugunov / Dmitrii S Kulbatskii / Milita V Kocharovskaya / Alexander S Paramonov / Maxim L Bychkov / Mikhail A Shulepko / ...Authors: Zakhar O Shenkarev / Yuri M Chesnokov / Maxim M Zaigraev / Anton O Chugunov / Dmitrii S Kulbatskii / Milita V Kocharovskaya / Alexander S Paramonov / Maxim L Bychkov / Mikhail A Shulepko / Dmitry E Nolde / Roman A Kamyshinsky / Evgeniy O Yablokov / Alexey S Ivanov / Mikhail P Kirpichnikov / Ekaterina N Lyukmanova / ![]() Abstract: Nicotinic acetylcholine receptor of α7 type (α7-nAChR) presented in the nervous and immune systems and epithelium is a promising therapeutic target for cognitive disfunctions and cancer treatment. ...Nicotinic acetylcholine receptor of α7 type (α7-nAChR) presented in the nervous and immune systems and epithelium is a promising therapeutic target for cognitive disfunctions and cancer treatment. Weak toxin from Naja kaouthia venom (WTX) is a non-conventional three-finger neurotoxin, targeting α7-nAChR with weak affinity. There are no data on interaction mode of non-conventional neurotoxins with nAChRs. Using α-bungarotoxin (classical three-finger neurotoxin with high affinity to α7-nAChR), we showed applicability of cryo-EM to study complexes of α7-nAChR extracellular ligand-binding domain (α7-ECD) with toxins. Using cryo-EM structure of the α7-ECD/WTX complex, together with NMR data on membrane active site in the WTX molecule and mutagenesis data, we reconstruct the structure of α7-nAChR/WTX complex in the membrane environment. WTX interacts at the entrance to the orthosteric site located at the receptor intersubunit interface and simultaneously forms the contacts with the membrane surface. WTX interaction mode with α7-nAChR significantly differs from α-bungarotoxin's one, which does not contact the membrane. Our study reveals the important role of the membrane for interaction of non-conventional neurotoxins with the nicotinic receptors. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 14.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.8 KB 17.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.3 KB | Display | ![]() |
Images | ![]() | 61.6 KB | ||
Masks | ![]() | 30.5 MB | ![]() | |
Others | ![]() ![]() | 28.3 MB 28.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 626.4 KB | Display | ![]() |
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Full document | ![]() | 626 KB | Display | |
Data in XML | ![]() | 13 KB | Display | |
Data in CIF | ![]() | 18 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
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Links
EMDB pages | ![]() ![]() |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.86 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Projections & Slices |
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Density Histograms |
-Half map: #2
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Projections & Slices |
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Density Histograms |
-Half map: #1
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Density Histograms |
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Sample components
-Entire : Alpha7-nAChR (Nicotinic acetylcholine receptor of alpha7 type) ex...
Entire | Name: Alpha7-nAChR (Nicotinic acetylcholine receptor of alpha7 type) extracellular ligand-binding domain |
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Components |
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-Supramolecule #1: Alpha7-nAChR (Nicotinic acetylcholine receptor of alpha7 type) ex...
Supramolecule | Name: Alpha7-nAChR (Nicotinic acetylcholine receptor of alpha7 type) extracellular ligand-binding domain type: complex / ID: 1 / Chimera: Yes / Parent: 0 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 10 KDa |
-Supramolecule #2: weak neurotoxin WTX
Supramolecule | Name: weak neurotoxin WTX / type: complex / ID: 2 / Chimera: Yes / Parent: 1 |
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Source (natural) | Organism: ![]() |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.15 mg/mL | |||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Support film - Material: GRAPHENE OXIDE / Support film - topology: HOLEY ARRAY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 5 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 0.026000000000000002 kPa | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Spherical aberration corrector: Cs corrector |
Image recording | Film or detector model: FEI FALCON II (4k x 4k) / Detector mode: INTEGRATING / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Digitization - Frames/image: 1-30 / Number grids imaged: 1 / Number real images: 1981 / Average exposure time: 1.5 sec. / Average electron dose: 80.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Calibrated defocus max: 3.0 µm / Calibrated defocus min: 1.0 µm / Calibrated magnification: 75000 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 0.01 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 75000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: RIGID BODY FIT |
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