9OUR

Native GABA-A receptor from rat cerebella, beta2-alpha1-beta2-alpha1-gamma2 subtype, in complex with GABA

これはPDB形式変換不可エントリーです。

9OUR の概要

• エントリーDOI: 10.2210/pdb9our/pdb
• EMDBエントリー: 70877
• 分子名称: Gamma-aminobutyric acid receptor subunit alpha-1, GAMMA-AMINO-BUTANOIC ACID, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• 機能のキーワード: neurotransmitter receptor, cys-loop receptor, ligand-gated ion channel, membrane protein
• 由来する生物種: Mus musculus (mouse); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 367756.18

構造登録者

Sun, C.,Gouaux, E. (登録日: 2025-05-29, 公開日: 2026-02-18)

主引用文献

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

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: 41650215
DOI: 10.1073/pnas.2524504123

実験手法

ELECTRON MICROSCOPY (2.84 Å)