9OUM
Native GABA-A receptor from rat cerebella, beta2-alpha1-beta1-alpha6-gamma2 subtype, in complex with GABA and PZ-II-029
This is a non-PDB format compatible entry.
Summary for 9OUM
| Entry DOI | 10.2210/pdb9oum/pdb |
| EMDB information | 70872 |
| Descriptor | Gamma-aminobutyric acid receptor subunit beta-1, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[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, GAMMA-AMINO-BUTANOIC ACID, ... (13 entities in total) |
| Functional Keywords | neurotransmitter receptor, cys-loop receptor, ligand-gated ion channel, membrane protein |
| Biological source | Mus musculus (mouse) More |
| Total number of polymer chains | 7 |
| Total formula weight | 319243.03 |
| Authors | |
| Primary citation | Sun, C.,Jahncke, J.N.,Wright, K.M.,Gouaux, E. Molecular assemblies and pharmacology of cerebellar GABA A receptors. Proc.Natl.Acad.Sci.USA, 123:e2524504123-e2524504123, 2026 Cited by PubMed 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 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. PubMed: 41650215DOI: 10.1073/pnas.2524504123 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.9 Å) |
Structure validation
Download full validation report
