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	Resolving native GABA receptor structures from the human brain.
ジャーナル・号・ページ	Nature, Vol. 638, Issue 8050, Page 562-568, Year 2025
掲載日	2025年1月22日
著者	Jia Zhou / Colleen M Noviello / Jinfeng Teng / Haley Moore / Bradley Lega / Ryan E Hibbs /
PubMed 要旨	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.
リンク	Nature / PubMed:39843743 / PubMed Central
手法	EM (単粒子)
解像度	2.9 - 3.74 Å
構造データ	45878 9crs EMDB-45878, PDB-9crs: Native human GABAA receptor of beta2-alpha1-beta2-alpha1-gamma2 assembly 手法: EM (単粒子) / 解像度: 2.9 Å 45884 9crv EMDB-45884, PDB-9crv: Native human GABAA receptor of beta2-alpha1-gamma2-beta2-alpha2 assembly 手法: EM (単粒子) / 解像度: 3.18 Å 45890 9csb EMDB-45890, PDB-9csb: Native human GABAA receptor of beta3-alpha1-beta2-alpha2-gamma2 assembly 手法: EM (単粒子) / 解像度: 3.34 Å 45894 9ct0 EMDB-45894, PDB-9ct0: Native human GABAA receptor of beta2-alpha1-beta2-alpha2-gamma2 assembly 手法: EM (単粒子) / 解像度: 3.19 Å 45908 9ctj EMDB-45908, PDB-9ctj: Native human GABAA receptor of beta2-alpha1-beta3-alpha2-gamma2 assembly 手法: EM (単粒子) / 解像度: 3.74 Å 45914 9ctp EMDB-45914, PDB-9ctp: Native human GABAA receptor of beta2-alpha1-beta2-alpha3-gamma2 assembly 手法: EM (単粒子) / 解像度: 3.62 Å 45920 9ctv EMDB-45920, PDB-9ctv: Native human GABAA receptor of beta2-alpha1-gamma2-beta1-alpha2 assembly 手法: EM (単粒子) / 解像度: 3.36 Å 45980 9cx7 EMDB-45980, PDB-9cx7: Native human GABAA receptor of beta3-alpha1-gamma2-beta3-alpha2 assembly 手法: EM (単粒子) / 解像度: 3.3 Å 45983 9cxa EMDB-45983, PDB-9cxa: Native human GABAA receptor of beta2-alpha1-beta3-alpha1-gamma2 assembly 手法: EM (単粒子) / 解像度: 3.04 Å 45984 9cxb EMDB-45984, PDB-9cxb: Native human GABAA receptor of beta2-alpha1-beta1-alpha2-gamma2 assembly 手法: EM (単粒子) / 解像度: 3.33 Å 45985 9cxc EMDB-45985, PDB-9cxc: Native human GABAA receptor of beta3-alpha1-gamma2-beta2-alpha2 assembly 手法: EM (単粒子) / 解像度: 3.3 Å 45986 9cxd EMDB-45986, PDB-9cxd: Native human GABAA receptor of beta2-alpha1-beta1-beta1-gamma2 assembly 手法: EM (単粒子) / 解像度: 3.36 Å 47132 9drx EMDB-47132, PDB-9drx: Human GABAA receptor of beta2-alpha1-beta2-alpha1-gamma2 subtype in complex with GABA plus Lamotrigine 手法: EM (単粒子) / 解像度: 2.95 Å
化合物	ChemComp-ABU: GAMMA-AMINO-BUTANOIC ACID / GABA / 神経伝達物質, 阻害剤YM ChemComp-PIO: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate / 1-O-(1-O,2-O-ジオクタノイル-L-グリセロ-3-ホスホ)-D-myo-イノシト-ル4,5-ビスりん酸 ChemComp-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / リン脂質YM ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-IYJ: (6M)-6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine / ラモトリギン
由来	homo sapiens (ヒト) mus musculus (ハツカネズミ) mus musculoides (ネズミ)
キーワード	MEMBRANE PROTEIN / Ion channels / heteropentamer / receptors / ihibitory. / MEMBRANE PROTEIN-IMMUNE SYSTEM complex / Receptor / Inhibitory. / Native / GABAA / ligand gated ion channel / neurotransmitter receptor