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- EMDB-7816: Human GABA-A receptor alpha1-beta2-gamma2 subtype in complex with... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-7816 | |||||||||
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Title | Human GABA-A receptor alpha1-beta2-gamma2 subtype in complex with GABA and flumazenil, conformation B | |||||||||
![]() | Main map sharpened to B factor -153 | |||||||||
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![]() | Ligand-gated ion channel / GABA-A receptor / Cys-loop receptor / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() benzodiazepine receptor activity / GABA receptor complex / cellular response to histamine / GABA receptor activation / inner ear receptor cell development / GABA-A receptor activity / GABA-gated chloride ion channel activity / GABA-A receptor complex / inhibitory synapse assembly / innervation ...benzodiazepine receptor activity / GABA receptor complex / cellular response to histamine / GABA receptor activation / inner ear receptor cell development / GABA-A receptor activity / GABA-gated chloride ion channel activity / GABA-A receptor complex / inhibitory synapse assembly / innervation / Signaling by ERBB4 / synaptic transmission, GABAergic / gamma-aminobutyric acid signaling pathway / postsynaptic specialization membrane / neurotransmitter receptor activity / adult behavior / cochlea development / chloride channel activity / chloride channel complex / transmembrane transporter complex / GABA-ergic synapse / regulation of postsynaptic membrane potential / chloride transmembrane transport / dendrite membrane / post-embryonic development / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / cytoplasmic vesicle membrane / chemical synaptic transmission / postsynapse / neuron projection / axon / synapse / extracellular exosome / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.86 Å | |||||||||
![]() | Zhu S / Noviello CM | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure of a human synaptic GABA receptor. Authors: Shaotong Zhu / Colleen M Noviello / Jinfeng Teng / Richard M Walsh / Jeong Joo Kim / Ryan E Hibbs / ![]() Abstract: Fast inhibitory neurotransmission in the brain is principally mediated by the neurotransmitter GABA (γ-aminobutyric acid) and its synaptic target, the type A GABA receptor (GABA receptor). ...Fast inhibitory neurotransmission in the brain is principally mediated by the neurotransmitter GABA (γ-aminobutyric acid) and its synaptic target, the type A GABA receptor (GABA receptor). Dysfunction of this receptor results in neurological disorders and mental illnesses including epilepsy, anxiety and insomnia. The GABA receptor is also a prolific target for therapeutic, illicit and recreational drugs, including benzodiazepines, barbiturates, anaesthetics and ethanol. Here we present high-resolution cryo-electron microscopy structures of the human α1β2γ2 GABA receptor, the predominant isoform in the adult brain, in complex with GABA and the benzodiazepine site antagonist flumazenil, the first-line clinical treatment for benzodiazepine overdose. The receptor architecture reveals unique heteromeric interactions for this important class of inhibitory neurotransmitter receptor. This work provides a template for understanding receptor modulation by GABA and benzodiazepines, and will assist rational approaches to therapeutic targeting of this receptor for neurological disorders and mental illness. | |||||||||
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 | ![]() | 5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 28.5 KB 28.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() ![]() | 9.3 KB 9.3 KB | Display Display | ![]() |
Images | ![]() ![]() ![]() ![]() | 183.3 KB 186.2 KB 205.5 KB 198.8 KB | ||
Filedesc metadata | ![]() | 8 KB | ||
Others | ![]() ![]() ![]() | 4.5 MB 51.9 MB 51.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6d6tMC ![]() 7817C ![]() 6d6uC 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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Annotation | Main map sharpened to B factor -153 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.07 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Main map sharpened to B factor -100
File | emd_7816_additional.map | ||||||||||||
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Annotation | Main map sharpened to B factor -100 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map 1
File | emd_7816_half_map_1.map | ||||||||||||
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Annotation | half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map 2
File | emd_7816_half_map_2.map | ||||||||||||
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Annotation | half map 2 | ||||||||||||
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Density Histograms |
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Sample components
+Entire : Human GABA-A receptor alpha1-beta2-gamma2 subtype in complex with...
+Supramolecule #1: Human GABA-A receptor alpha1-beta2-gamma2 subtype in complex with...
+Macromolecule #1: Gamma-aminobutyric acid receptor subunit beta-2,Gamma-aminobutyri...
+Macromolecule #2: Gamma-aminobutyric acid receptor subunit alpha-1,Gamma-aminobutyr...
+Macromolecule #3: Human GABA-A receptor subunit gamma-2
+Macromolecule #4: Kappa Fab Light Chain
+Macromolecule #5: IgG2b Fab Heavy Chain
+Macromolecule #9: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #10: GAMMA-AMINO-BUTANOIC ACID
+Macromolecule #11: CHOLESTEROL HEMISUCCINATE
+Macromolecule #12: ethyl 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a][1,4]b...
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
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: 200 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 80 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 39.0 kPa Details: Sample was glow discharged at 30 mA for 80 seconds using a PELCO easiGLow | |||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV / Details: 3 seconds blot time. |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Temperature | Min: 80.0 K / Max: 90.0 K |
Specialist optics | Energy filter - Name: GIF Quantum LS / Energy filter - Lower energy threshold: -10 eV / Energy filter - Upper energy threshold: 10 eV |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Number grids imaged: 2 / Number real images: 5594 / Average exposure time: 10.0 sec. / Average electron dose: 47.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 70.0 µm / Calibrated magnification: 46730 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 4.5 µm / Nominal defocus min: 0.5 µm |
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: AB INITIO MODEL |
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Output model | ![]() PDB-6d6t: |