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Yorodumi- EMDB-20489: Human alpha3beta4 nicotinic acetylcholine receptor in complex wit... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20489 | |||||||||||||||||||||
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Title | Human alpha3beta4 nicotinic acetylcholine receptor in complex with nicotine in saposin nanodiscs without CHS | |||||||||||||||||||||
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Sample |
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Biological species | Homo sapiens (human) | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.7 Å | |||||||||||||||||||||
Authors | Gharpure A / Teng J / Zhuang Y / Noviello CM / Walsh RM / Cabuco R / Howard RJ / Zaveri NT / Lindahl E / Hibbs RE | |||||||||||||||||||||
Funding support | United States, 6 items
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Citation | Journal: Neuron / Year: 2019 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 |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_20489.map.gz | 9.1 MB | EMDB map data format | |
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Header (meta data) | emd-20489-v30.xml emd-20489.xml | 18 KB 18 KB | Display Display | EMDB header |
Images | emd_20489.png | 28.5 KB | ||
Others | emd_20489_half_map_1.map.gz emd_20489_half_map_2.map.gz | 80.7 MB 80.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20489 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20489 | HTTPS FTP |
-Validation report
Summary document | emd_20489_validation.pdf.gz | 705.9 KB | Display | EMDB validaton report |
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Full document | emd_20489_full_validation.pdf.gz | 705.5 KB | Display | |
Data in XML | emd_20489_validation.xml.gz | 13 KB | Display | |
Data in CIF | emd_20489_validation.cif.gz | 15.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20489 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20489 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_20489.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.89 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_20489_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_20489_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Human alpha3beta4 nicotinic receptor in complex with Fab fragment...
Entire | Name: Human alpha3beta4 nicotinic receptor in complex with Fab fragments and bound to nicotine |
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Components |
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-Supramolecule #1: Human alpha3beta4 nicotinic receptor in complex with Fab fragment...
Supramolecule | Name: Human alpha3beta4 nicotinic receptor in complex with Fab fragments and bound to nicotine type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 Details: Fab fragments generated by proteolytic cleavage of IgG antibody |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-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. |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Detector mode: SUPER-RESOLUTION / Number real images: 1020 / Average exposure time: 2.0 sec. / Average electron dose: 64.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated magnification: 57013 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |