EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Molecular assemblies and pharmacology of cerebellar GABA receptors.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 123, Issue 6, Page e2524504123, Year 2026
掲載日	2026年2月10日
著者	Chang Sun / Jennifer N Jahncke / Kevin M Wright / Eric Gouaux /
PubMed 要旨	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.
リンク	Proc Natl Acad Sci U S A / PubMed:41650215 / PubMed Central
手法	EM (単粒子)
解像度	2.74 - 2.93 Å
構造データ	70872 9oum EMDB-70872, PDB-9oum: Native GABA-A receptor from rat cerebella, beta2-alpha1-beta1-alpha6-gamma2 subtype, in complex with GABA and PZ-II-029 手法: EM (単粒子) / 解像度: 2.9 Å 70873 9oun EMDB-70873, PDB-9oun: Native GABA-A receptor from rat cerebella, beta2-alpha1-beta2-alpha1-gamma2 subtype, in complex with GABA and PZ-II-029 手法: EM (単粒子) / 解像度: 2.74 Å 70874 9ouo EMDB-70874, PDB-9ouo: Native GABA-A receptor from rat cerebella, beta1-alpha1-beta1-alpha1-gamma2 subtype, in complex with GABA and PZ-II-029 手法: EM (単粒子) / 解像度: 2.92 Å 70875 9oup EMDB-70875, PDB-9oup: Native GABA-A receptor from rat cerebella, beta2-alpha1-beta1-alpha6-gamma2 subtype, in complex with GABA 手法: EM (単粒子) / 解像度: 2.82 Å 70876 9ouq EMDB-70876, PDB-9ouq: Native GABA-A receptor from rat cerebella, beta1-alpha1-beta2-alpha1-gamma2 subtype, in complex with GABA 手法: EM (単粒子) / 解像度: 2.89 Å 70877 9our EMDB-70877, PDB-9our: Native GABA-A receptor from rat cerebella, beta2-alpha1-beta2-alpha1-gamma2 subtype, in complex with GABA 手法: EM (単粒子) / 解像度: 2.84 Å 70889 9ov4 EMDB-70889, PDB-9ov4: Native GABA-A receptor from rat cerebella, beta1-alpha1-beta2-alpha1-gamma2 subtype, in complex with GABA and PZ-II-029 手法: EM (単粒子) / 解像度: 2.93 Å
化合物	ChemComp-ABU: GAMMA-AMINO-BUTANOIC ACID / 神経伝達物質, 阻害剤YM ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose PDB-1cep*: Unknown entry
由来	rattus norvegicus (ドブネズミ) mus musculus (ハツカネズミ)
キーワード	MEMBRANE PROTEIN / neurotransmitter receptor / cys-loop receptor / ligand-gated ion channel