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Yorodumi- EMDB-70875: Native GABA-A receptor from rat cerebella, beta2-alpha1-beta1-alp... -
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Basic information
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| Title | Native GABA-A receptor from rat cerebella, beta2-alpha1-beta1-alpha6-gamma2 subtype, in complex with GABA | |||||||||
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Keywords | neurotransmitter receptor / cys-loop receptor / ligand-gated ion channel / MEMBRANE PROTEIN | |||||||||
| Function / homology | Function and homology informationcerebellar Golgi cell to granule cell synapse / diazepam binding / inhibitory extracellular ligand-gated monoatomic ion channel activity / GABA receptor activation / ovulation cycle / : / response to methamphetamine hydrochloride / inhibitory synapse / response to auditory stimulus / GABA receptor complex ...cerebellar Golgi cell to granule cell synapse / diazepam binding / inhibitory extracellular ligand-gated monoatomic ion channel activity / GABA receptor activation / ovulation cycle / : / response to methamphetamine hydrochloride / inhibitory synapse / response to auditory stimulus / GABA receptor complex / GABA receptor binding / monoatomic anion channel activity / cellular response to histamine / inner ear receptor cell development / inhibitory synapse assembly / GABA-gated chloride ion channel activity / GABA-A receptor complex / GABA-A receptor activity / heterocyclic compound binding / innervation / chloride transport / response to anesthetic / postsynaptic specialization membrane / neuronal cell body membrane / gamma-aminobutyric acid signaling pathway / synaptic transmission, GABAergic / central nervous system neuron development / adult behavior / cellular response to zinc ion / ligand-gated monoatomic ion channel activity / chloride channel activity / cochlea development / chloride channel complex / neuron development / monoatomic ion transport / presynaptic active zone membrane / dendrite membrane / response to progesterone / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / chloride transmembrane transport / cytoplasmic vesicle membrane / hippocampal mossy fiber to CA3 synapse / post-embryonic development / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / GABA-ergic synapse / response to toxic substance / Schaffer collateral - CA1 synapse / nuclear envelope / presynaptic membrane / dendritic spine / response to ethanol / chemical synaptic transmission / postsynaptic membrane / receptor complex / postsynapse / axon / dendrite / protein-containing complex binding / glutamatergic synapse / cell surface / plasma membrane Similarity search - Function | |||||||||
| Biological species | ![]() ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.82 Å | |||||||||
Authors | Sun C / Gouaux E | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2026Title: Molecular assemblies and pharmacology of cerebellar GABA receptors. Authors: Chang Sun / Jennifer N Jahncke / Kevin M Wright / Eric Gouaux / ![]() Abstract: GABA receptors (GABARs) mediate fast inhibitory neurotransmission in the brain and are assembled from 19 subunit isoforms into multiple pentameric assemblies. Although α1-containing GABARs are ...GABA receptors (GABARs) mediate fast inhibitory neurotransmission in the brain and are assembled from 19 subunit isoforms into multiple pentameric assemblies. Although α1-containing GABARs are broadly expressed and are pharmacologically important, the molecular diversity of native α1-based assemblies in specific brain regions remains incompletely understood. Here, we use immunofluorescence, mass spectrometry, and cryogenic electron microscopy (cryo-EM) to characterize the spatial distribution, subunit composition, and structural architecture of native α1-containing GABARs in the rat cerebellum. Confocal microscopy reveals robust colocalization of α1 and γ2 subunits across cerebellar layers, including prominent labeling at glomerular synapses. Biochemical purification and proteomic analysis identify a range of α, β, and γ subunits, along with abundant α6 and δ subunits. Using cryo-EM and automated subunit identification, we resolve eight α1-containing receptor assemblies, including the first structure of α6-containing receptors. We further determine the binding mode of the α6-selective pyrazoloquinolinone modulator PZ-II-029 at the α/γ interface, showing ligand-induced expansion of the entire extracellular domain (ECD). Together, our study defines the structure and subunit composition of the α1-containing cerebellar GABARs and elaborates the molecular interactions between native receptors and pyrazoloquinolinone, thereby laying the groundwork for brain region and subunit-specific pharmacology. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_70875.map.gz | 89 MB | EMDB map data format | |
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| Header (meta data) | emd-70875-v30.xml emd-70875.xml | 26.1 KB 26.1 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_70875_fsc.xml | 11.9 KB | Display | FSC data file |
| Images | emd_70875.png | 88.9 KB | ||
| Filedesc metadata | emd-70875.cif.gz | 7.9 KB | ||
| Others | emd_70875_additional_1.map.gz emd_70875_half_map_1.map.gz emd_70875_half_map_2.map.gz | 151 MB 165.2 MB 165.2 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-70875 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-70875 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9oupMC ![]() 9oumC ![]() 9ounC ![]() 9ouoC ![]() 9ouqC ![]() 9ourC ![]() 9ov4C M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_70875.map.gz / Format: CCP4 / Size: 178 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: 0.857 Å | ||||||||||||||||||||||||||||||||||||
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Additional map: map sharpened with EMReady
| File | emd_70875_additional_1.map | ||||||||||||
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| Annotation | map sharpened with EMReady | ||||||||||||
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-Half map: #2
| File | emd_70875_half_map_1.map | ||||||||||||
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-Half map: #1
| File | emd_70875_half_map_2.map | ||||||||||||
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Sample components
+Entire : Native GABA-A receptor from rat cerebella, beta2-alpha1-beta1-alp...
+Supramolecule #1: Native GABA-A receptor from rat cerebella, beta2-alpha1-beta1-alp...
+Macromolecule #1: Gamma-aminobutyric acid receptor subunit alpha-1
+Macromolecule #2: Gamma-aminobutyric acid receptor subunit beta-1
+Macromolecule #3: Gamma-aminobutyric acid receptor subunit alpha-6
+Macromolecule #4: Gamma-aminobutyric acid receptor subunit gamma-2
+Macromolecule #5: Gamma-aminobutyric acid receptor subunit beta-2
+Macromolecule #6: 8E3 fab heavy chain
+Macromolecule #7: 8E3 fab light chain
+Macromolecule #11: GAMMA-AMINO-BUTANOIC ACID
+Macromolecule #12: 2-acetamido-2-deoxy-beta-D-glucopyranose
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Concentration | 0.05 mg/mL |
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| Buffer | pH: 8 |
| Vitrification | Cryogen name: ETHANE-PROPANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 43.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.2 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi



Keywords
Authors
United States, 1 items
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Processing
FIELD EMISSION GUN

