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Yorodumi- PDB-6pv8: Human alpha3beta4 nicotinic acetylcholine receptor in complex wit... -
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Open data
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Basic information
| Entry | Database: PDB / ID: 6pv8 | |||||||||||||||||||||
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| Title | Human alpha3beta4 nicotinic acetylcholine receptor in complex with AT-1001 | |||||||||||||||||||||
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Keywords | MEMBRANE PROTEIN / Ligand-gated ion channel / Nicotinic acetylcholine receptor / Cys-loop receptor | |||||||||||||||||||||
| Function / homology | Function and homology informationregulation 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 / cholinergic synapse / response to acetylcholine / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine receptor activity / regulation of neurotransmitter secretion ...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 / cholinergic synapse / response to acetylcholine / Highly calcium permeable postsynaptic nicotinic acetylcholine receptors / acetylcholine receptor activity / regulation of neurotransmitter secretion / acetylcholine-gated channel complex / regulation of smooth muscle contraction / behavioral response to nicotine / neuromuscular synaptic transmission / acetylcholine-gated monoatomic cation-selective channel activity / cation channel complex / acetylcholine binding / synaptic transmission, cholinergic / acetylcholine receptor signaling pathway / neurotransmitter receptor complex / postsynaptic specialization membrane / ligand-gated monoatomic ion channel activity / regulation of dendrite morphogenesis / tertiary granule membrane / smooth muscle contraction / plasma membrane raft / membrane depolarization / neuronal action potential / specific granule membrane / monoatomic ion transport / response to nicotine / regulation of membrane potential / excitatory postsynaptic potential / 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 / heme binding / dendrite / synapse / Neutrophil degranulation / nucleolus / endoplasmic reticulum / Golgi apparatus / signal transduction / membrane / plasma membrane / cytosol Similarity search - Function | |||||||||||||||||||||
| Biological species | Homo sapiens (human)![]() ![]() | |||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.87 Å | |||||||||||||||||||||
Authors | 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 | United States, 6items
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Citation | Journal: Neuron / Year: 2019Title: 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. | |||||||||||||||||||||
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Structure visualization
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| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 6pv8.cif.gz | 474.7 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb6pv8.ent.gz | 372.2 KB | Display | PDB format |
| PDBx/mmJSON format | 6pv8.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 6pv8_validation.pdf.gz | 2.5 MB | Display | wwPDB validaton report |
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| Full document | 6pv8_full_validation.pdf.gz | 2.5 MB | Display | |
| Data in XML | 6pv8_validation.xml.gz | 78.8 KB | Display | |
| Data in CIF | 6pv8_validation.cif.gz | 113.1 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pv/6pv8 ftp://data.pdbj.org/pub/pdb/validation_reports/pv/6pv8 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 20488MC ![]() 6pv7C M: map data used to model this data C: citing same article ( |
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| Similar structure data |
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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.) Homo sapiens (human), (gene. exp.) ![]() Gene: CHRNA3, NACHRA3, CWJ32_12820 / Plasmid: pEZT-BM / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / Variant (production host): GNTI- / References: UniProt: P32297, UniProt: A0A3W4NZ06#2: Protein | Mass: 61337.594 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human), (gene. exp.) ![]() Gene: CHRNB4, CWJ32_12820 / Plasmid: pEZT-BM / Production host: Homo sapiens (human) / Variant (production host): GNTI- / References: UniProt: P30926, UniProt: A0A3W4NZ06 |
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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 #10: Sugar | ChemComp-NAG / |
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-Non-polymers , 4 types, 21 molecules 






| #8: Chemical | | #9: Chemical | ChemComp-Y01 / #11: Chemical | ChemComp-NA / | #12: 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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| Source (recombinant) |
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| Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Calibrated magnification: 59523 X / Cs: 2.7 mm |
| Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
| Image recording | Average exposure time: 8 sec. / Electron dose: 48 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 3008 |
| EM imaging optics | Energyfilter name: GIF Quantum LS / Energyfilter slit width: 20 eV |
| Image scans | Movie frames/image: 20 |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||
| Particle selection | Num. of particles selected: 548045 | ||||||||||||||||||||||||||||||
| Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.87 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 93080 / Algorithm: BACK PROJECTION / Symmetry type: POINT | ||||||||||||||||||||||||||||||
| Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |
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Homo sapiens (human)


United States, 6items
Citation
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