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- EMDB-45983: Native human GABAA receptor of beta2-alpha1-beta3-alpha1-gamma2 a... -
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Open data
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Basic information
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Title | Native human GABAA receptor of beta2-alpha1-beta3-alpha1-gamma2 assembly | |||||||||
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![]() | Native / GABAA / ligand gated ion channel / neurotransmitter receptor / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() benzodiazepine receptor activity / inner ear receptor cell development / GABA receptor complex / innervation / cellular response to histamine / GABA receptor activation / GABA-A receptor activity / GABA-gated chloride ion channel activity / GABA-A receptor complex / inhibitory synapse assembly ...benzodiazepine receptor activity / inner ear receptor cell development / GABA receptor complex / innervation / cellular response to histamine / GABA receptor activation / GABA-A receptor activity / GABA-gated chloride ion channel activity / GABA-A receptor complex / inhibitory synapse assembly / gamma-aminobutyric acid signaling pathway / postsynaptic specialization membrane / synaptic transmission, GABAergic / cochlea development / chloride channel activity / adult behavior / roof of mouth development / Signaling by ERBB4 / chloride channel complex / dendrite membrane / cytoplasmic vesicle membrane / chloride transmembrane transport / post-embryonic development / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / GABA-ergic synapse / chemical synaptic transmission / dendritic spine / postsynaptic membrane / postsynapse / axon / signal transduction / extracellular exosome / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.04 Å | |||||||||
![]() | Zhou J / Hibbs RE / Noviello CM | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Resolving native GABA receptor structures from the human brain. Authors: Jia Zhou / Colleen M Noviello / Jinfeng Teng / Haley Moore / Bradley Lega / Ryan E Hibbs / ![]() Abstract: Type A GABA (γ-aminobutyric acid) receptors (GABA receptors) mediate most fast inhibitory signalling in the brain and are targets for drugs that treat epilepsy, anxiety, depression and insomnia and ...Type A GABA (γ-aminobutyric acid) receptors (GABA receptors) mediate most fast inhibitory signalling in the brain and are targets for drugs that treat epilepsy, anxiety, depression and insomnia and for anaesthetics. These receptors comprise a complex array of 19 related subunits, which form pentameric ligand-gated ion channels. The composition and structure of native GABA receptors in the human brain have been inferred from subunit localization in tissue, functional measurements and structural analysis from recombinant expression and in mice. However, the arrangements of subunits that co-assemble physiologically in native human GABA receptors remain unknown. Here we isolated α1 subunit-containing GABA receptors from human patients with epilepsy. Using cryo-electron microscopy, we defined a set of 12 native subunit assemblies and their 3D structures. We address inconsistencies between previous native and recombinant approaches, and reveal details of previously undefined subunit interfaces. Drug-like densities in a subset of these interfaces led us to uncover unexpected activity on the GABA receptor of antiepileptic drugs and resulted in localization of one of these drugs to the benzodiazepine-binding site. Proteomics and further structural analysis suggest interactions with the auxiliary subunits neuroligin 2 and GARLH4, which localize and modulate GABA receptors at inhibitory synapses. This work provides a structural foundation for understanding GABA receptor signalling and targeted pharmacology in the human brain. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 28.5 KB 28.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 8.4 KB | Display | ![]() |
Images | ![]() | 78.8 KB | ||
Masks | ![]() | 64 MB | ![]() | |
Filedesc metadata | ![]() | 8.5 KB | ||
Others | ![]() ![]() ![]() | 32.2 MB 59.4 MB 59.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9cxaMC ![]() 9crsC ![]() 9crvC ![]() 9csbC ![]() 9ct0C ![]() 9ctjC ![]() 9ctpC ![]() 9ctvC ![]() 9cx7C ![]() 9cxbC ![]() 9cxcC ![]() 9cxdC ![]() 9drxC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.935 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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-Additional map: #1
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-Half map: #2
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-Half map: #1
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Sample components
+Entire : Native GABAA receptor purified from human brain
+Supramolecule #1: Native GABAA receptor purified from human brain
+Macromolecule #1: Gamma-aminobutyric acid receptor subunit beta-2
+Macromolecule #2: Gamma-aminobutyric acid receptor subunit alpha-1
+Macromolecule #3: Gamma-aminobutyric acid receptor subunit beta-3
+Macromolecule #4: Gamma-aminobutyric acid receptor subunit gamma-2
+Macromolecule #5: Kappa Fab_1F4 Light Chain
+Macromolecule #6: IgG2b Fab_1F4 Heavy Chain
+Macromolecule #10: GAMMA-AMINO-BUTANOIC ACID
+Macromolecule #11: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(o...
+Macromolecule #12: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
+Macromolecule #13: 2-acetamido-2-deoxy-beta-D-glucopyranose
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 4 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |