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- PDB-6pv7: Human alpha3beta4 nicotinic acetylcholine receptor in complex wit... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6pv7 | |||||||||||||||||||||
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Title | Human alpha3beta4 nicotinic acetylcholine receptor in complex with nicotine | |||||||||||||||||||||
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![]() | MEMBRANE PROTEIN / Ligand-gated ion channel / Nicotinic acetylcholine receptor / Cys-loop receptor | |||||||||||||||||||||
Function / homology | ![]() regulation of acetylcholine secretion, neurotransmission / positive regulation of transmission of nerve impulse / Highly sodium permeable postsynaptic acetylcholine nicotinic receptors / Highly calcium permeable nicotinic acetylcholine receptors / synaptic transmission involved in micturition / response to acetylcholine / cholinergic synapse / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine receptor activity / acetylcholine-gated channel complex ...regulation of acetylcholine secretion, neurotransmission / positive regulation of transmission of nerve impulse / Highly sodium permeable postsynaptic acetylcholine nicotinic receptors / Highly calcium permeable nicotinic acetylcholine receptors / synaptic transmission involved in micturition / response to acetylcholine / cholinergic synapse / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine receptor activity / acetylcholine-gated channel complex / regulation of neurotransmitter secretion / regulation of smooth muscle contraction / neuromuscular synaptic transmission / behavioral response to nicotine / acetylcholine-gated monoatomic cation-selective channel activity / cation channel complex / acetylcholine binding / synaptic transmission, cholinergic / acetylcholine receptor signaling pathway / neurotransmitter receptor complex / ligand-gated monoatomic ion channel activity / postsynaptic specialization membrane / regulation of dendrite morphogenesis / tertiary granule membrane / plasma membrane raft / smooth muscle contraction / membrane depolarization / neuronal action potential / specific granule membrane / monoatomic ion transport / excitatory postsynaptic potential / regulation of membrane potential / response to nicotine / locomotory behavior / nervous system development / monoatomic ion transmembrane transport / chemical synaptic transmission / postsynaptic membrane / periplasmic space / electron transfer activity / neuron projection / nuclear speck / ciliary basal body / iron ion binding / neuronal cell body / intracellular membrane-bounded organelle / synapse / heme binding / dendrite / Neutrophil degranulation / nucleolus / endoplasmic reticulum / Golgi apparatus / signal transduction / membrane / plasma membrane / cytosol Similarity search - Function | |||||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.34 Å | |||||||||||||||||||||
![]() | Gharpure, A. / Teng, J. / Zhuang, Y. / Noviello, C.M. / Walsh, R.M. / Cabuco, R. / Howard, R.J. / Zaveri, N.T. / Lindahl, E. / Hibbs, R.E. | |||||||||||||||||||||
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 | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 472.5 KB | Display | ![]() |
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PDB format | ![]() | 373.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 2.5 MB | Display | ![]() |
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Full document | ![]() | 2.5 MB | Display | |
Data in XML | ![]() | 78.5 KB | Display | |
Data in CIF | ![]() | 113 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 20487MC ![]() 6pv8C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Fusion protein of Neuronal acetylcholine receptor subunit ... , 2 types, 5 molecules ADBCE
#1: Protein | Mass: 60087.363 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: CHRNA3, NACHRA3, CWJ32_12820 / Plasmid: pEZT-BM / Cell line (production host): HEK293 / Production host: ![]() #2: Protein | Mass: 61337.594 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: CHRNB4, CWJ32_12820 / Plasmid: pEZT-BM / Cell line (production host): HEK293 / Production host: ![]() |
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-Antibody , 2 types, 4 molecules FHGI
#3: Antibody | Mass: 23396.051 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #4: Antibody | Mass: 23401.861 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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-Sugars , 4 types, 16 molecules 
#5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #7: Polysaccharide | Source method: isolated from a genetically manipulated source #11: Sugar | ChemComp-NAG / |
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-Non-polymers , 5 types, 22 molecules 








#8: Chemical | #9: Chemical | ChemComp-Y01 / #10: Chemical | ChemComp-NA / | #12: Chemical | ChemComp-DD9 / | #13: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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Has protein modification | Y |
-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 |
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Source (natural) |
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Source (recombinant) | Organism: ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 6 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: 4 second blot |
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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: BRIGHT FIELD / Calibrated magnification: 46730 X / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 10 sec. / Electron dose: 47 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 5053 |
EM imaging optics | Energyfilter name: GIF Quantum LS / Energyfilter slit width: 20 eV |
Image scans | Movie frames/image: 40 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 705401 | ||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.34 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 112737 / Algorithm: BACK PROJECTION / Symmetry type: POINT | ||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |