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- EMDB-20488: Human alpha3beta4 nicotinic acetylcholine receptor in complex wit... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-20488 | |||||||||||||||||||||
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Title | Human alpha3beta4 nicotinic acetylcholine receptor in complex with AT-1001 | |||||||||||||||||||||
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Function / homology | ![]() regulation of acetylcholine secretion, neurotransmission / synaptic transmission involved in micturition / Highly sodium permeable postsynaptic acetylcholine nicotinic receptors / positive regulation of transmission of nerve impulse / Highly calcium permeable nicotinic acetylcholine receptors / response to acetylcholine / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine-gated channel complex / regulation of smooth muscle contraction / cholinergic synapse ...regulation of acetylcholine secretion, neurotransmission / synaptic transmission involved in micturition / Highly sodium permeable postsynaptic acetylcholine nicotinic receptors / positive regulation of transmission of nerve impulse / Highly calcium permeable nicotinic acetylcholine receptors / response to acetylcholine / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine-gated channel complex / regulation of smooth muscle contraction / cholinergic synapse / regulation of neurotransmitter secretion / behavioral response to nicotine / excitatory extracellular ligand-gated monoatomic ion channel activity / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||||||||||||||
Method | ![]() ![]() | |||||||||||||||||||||
![]() | Gharpure A / Teng J / Zhuang Y / Noviello CM / Walsh RM / Cabuco R / Howard RJ / Zaveri NT / Lindahl E / Hibbs RE | |||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Agonist Selectivity and Ion Permeation in the α3β4 Ganglionic Nicotinic Receptor. Authors: Anant Gharpure / Jinfeng Teng / Yuxuan Zhuang / Colleen M Noviello / Richard M Walsh / Rico Cabuco / Rebecca J Howard / Nurulain T Zaveri / Erik Lindahl / Ryan E Hibbs / ![]() ![]() Abstract: Nicotinic acetylcholine receptors are pentameric ion channels that mediate fast chemical neurotransmission. The α3β4 nicotinic receptor subtype forms the principal relay between the central and ...Nicotinic acetylcholine receptors are pentameric ion channels that mediate fast chemical neurotransmission. The α3β4 nicotinic receptor subtype forms the principal relay between the central and peripheral nervous systems in the autonomic ganglia. This receptor is also expressed focally in brain areas that affect reward circuits and addiction. Here, we present structures of the α3β4 nicotinic receptor in lipidic and detergent environments, using functional reconstitution to define lipids appropriate for structural analysis. The structures of the receptor in complex with nicotine, as well as the α3β4-selective ligand AT-1001, complemented by molecular dynamics, suggest principles of agonist selectivity. The structures further reveal much of the architecture of the intracellular domain, where mutagenesis experiments and simulations define residues governing ion conductance. | |||||||||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 11.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 28.2 KB 28.2 KB | Display Display | ![]() |
Images | ![]() | 30.4 KB | ||
Others | ![]() ![]() | 80.7 MB 80.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6pv8MC ![]() 6pv7C M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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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Voxel size | X=Y=Z: 0.84 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: #2
File | emd_20488_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_20488_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
+Entire : Human alpha3beta4 nicotinic receptor in complex with Fab fragment...
+Supramolecule #1: Human alpha3beta4 nicotinic receptor in complex with Fab fragment...
+Supramolecule #2: Human alpha3beta4 nicotinic acetylcholine receptor
+Supramolecule #3: Neuronal acetylcholine receptor subunit alpha-3
+Supramolecule #4: Neuronal acetylcholine receptor subunit beta-4
+Supramolecule #5: IgG2b/kappa antibody
+Supramolecule #6: IgG2b heavy chain
+Supramolecule #7: Kappa Fab light chain
+Macromolecule #1: Fusion protein of Neuronal acetylcholine receptor subunit alpha-3...
+Macromolecule #2: Fusion protein of Neuronal acetylcholine receptor subunit beta-4 ...
+Macromolecule #3: IgG2b Fab heavy chain
+Macromolecule #4: Kappa Fab light chain
+Macromolecule #8: (3-endo)-N-(2-bromophenyl)-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine
+Macromolecule #9: CHOLESTEROL HEMISUCCINATE
+Macromolecule #10: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #11: SODIUM ION
+Macromolecule #12: water
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Concentration | 6 mg/mL | |||||||||||||||||||||
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Buffer | pH: 7.4 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE | |||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV / Details: 4 second blot. |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Calibrated magnification: 59523 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Specialist optics | Energy filter - Name: GIF Quantum LS / Energy filter - Slit width: 20 eV |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Number real images: 3008 / Average exposure time: 8.0 sec. / Average electron dose: 48.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Particle selection | Number selected: 548045 |
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CTF correction | Software - Name: Gctf |
Startup model | Type of model: OTHER / Details: De novo initial model from Relion |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: RELION |
Final 3D classification | Software - Name: RELION |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: RELION |
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Algorithm: BACK PROJECTION / Resolution.type: BY AUTHOR / Resolution: 3.87 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 93080 |
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL |
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Output model | ![]() PDB-6pv8: |