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	Differential assembly diversifies GABA receptor structures and signalling.
ジャーナル・号・ページ	Nature, Vol. 604, Issue 7904, Page 190-194, Year 2022
掲載日	2022年3月30日
著者	Andrija Sente / Rooma Desai / Katerina Naydenova / Tomas Malinauskas / Youssef Jounaidi / Jonas Miehling / Xiaojuan Zhou / Simonas Masiulis / Steven W Hardwick / Dimitri Y Chirgadze / Keith W Miller / A Radu Aricescu /
PubMed 要旨	Type A γ-aminobutyric acid receptors (GABARs) are pentameric ligand-gated chloride channels that mediate fast inhibitory signalling in neural circuits and can be modulated by essential medicines ...Type A γ-aminobutyric acid receptors (GABARs) are pentameric ligand-gated chloride channels that mediate fast inhibitory signalling in neural circuits and can be modulated by essential medicines including general anaesthetics and benzodiazepines. Human GABAR subunits are encoded by 19 paralogous genes that can, in theory, give rise to 495,235 receptor types. However, the principles that govern the formation of pentamers, the permutational landscape of receptors that may emerge from a subunit set and the effect that this has on GABAergic signalling remain largely unknown. Here we use cryogenic electron microscopy to determine the structures of extrasynaptic GABARs assembled from α4, β3 and δ subunits, and their counterparts incorporating γ2 instead of δ subunits. In each case, we identified two receptor subtypes with distinct stoichiometries and arrangements, all four differing from those previously observed for synaptic, α1-containing receptors. This, in turn, affects receptor responses to physiological and synthetic modulators by creating or eliminating ligand-binding sites at subunit interfaces. We provide structural and functional evidence that selected GABAR arrangements can act as coincidence detectors, simultaneously responding to two neurotransmitters: GABA and histamine. Using assembly simulations and single-cell RNA sequencing data, we calculated the upper bounds for receptor diversity in recombinant systems and in vivo. We propose that differential assembly is a pervasive mechanism for regulating the physiology and pharmacology of GABARs.
リンク	Nature / PubMed:35355020 / PubMed Central
手法	EM (単粒子)
解像度	2.5 - 3.4 Å
構造データ	14067 7qn5 EMDB-14067, PDB-7qn5: Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in complex with nanobody Nb25 手法: EM (単粒子) / 解像度: 2.5 Å 14068 7qn6 EMDB-14068, PDB-7qn6: Cryo-EM structure of human full-length beta3delta GABA(A)R in complex with nanobody Nb25 手法: EM (単粒子) / 解像度: 2.9 Å 14069 7qn7 EMDB-14069, PDB-7qn7: Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in complex with GABA, histamine and nanobody Nb25 手法: EM (単粒子) / 解像度: 3.0 Å 14070 7qn8 EMDB-14070, PDB-7qn8: Cryo-EM structure of human full-length beta3delta GABA(A)R in complex with histamine and nanobody Nb25 手法: EM (単粒子) / 解像度: 3.1 Å 14071 7qn9 EMDB-14071, PDB-7qn9: Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in complex with GABA, histamine and nanobody Nb25 in a pre-open/closed state 手法: EM (単粒子) / 解像度: 2.9 Å 14072 7qna EMDB-14072, PDB-7qna: Cryo-EM structure of human full-length alpha4beta3gamma2 GABA(A)R in complex with GABA and nanobody Nb25 手法: EM (単粒子) / 解像度: 3.0 Å 14073 7qnb EMDB-14073, PDB-7qnb: Cryo-EM structure of human full-length beta3gamma2 GABA(A)R in complex with GABA and nanobody Nb25 手法: EM (単粒子) / 解像度: 3.1 Å 14074 7qnc EMDB-14074, PDB-7qnc: Cryo-EM structure of human full-length extrasynaptic alpha4beta3delta GABA(A)R in complex with THIP (gaboxadol), histamine and nanobody Nb25 手法: EM (単粒子) / 解像度: 2.9 Å 14075 7qnd EMDB-14075, PDB-7qnd: Cryo-EM structure of human full-length extrasynaptic beta3delta GABA(A)R in complex with THIP (gaboxadol), histamine and nanobody Nb25 手法: EM (単粒子) / 解像度: 3.4 Å 14076 7qne EMDB-14076, PDB-7qne: Cryo-EM structure of human full-length synaptic alpha1beta3gamma2 GABA(A)R in complex with Ro15-4513 and megabody Mb38 手法: EM (単粒子) / 解像度: 2.7 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン ChemComp-PX6: 1,2-DIPALMITOYL-SN-GLYCERO-3-PHOSPHATE ChemComp-D10: DECANE / デカン / デカン ChemComp-OCT: N-OCTANE / オクタン / オクタン ChemComp-EPE: 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID / HEPES / pH緩衝剤YM / HEPES ChemComp-CL: Unknown entry / クロリド / 塩化物 ChemComp-HOH: WATER / 水 ChemComp-ABU: GAMMA-AMINO-BUTANOIC ACID / GABA / 神経伝達物質, 阻害剤YM / Γ-アミノ酪酸 ChemComp-R16: HEXADECANE / ヘキサデカン / ヘキサデカン ChemComp-HSM: HISTAMINE / ヒスタミン / 神経伝達物質, ホルモンYM / ヒスタミン ChemComp-EI7: 4,5,6,7-tetrahydro-[1,2]oxazolo[5,4-c]pyridin-3-one / THIP / alkaloidYM / Gaboxadol 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-EIE: ethyl 8-[(azanylidene-$l^{4}-azanylidene)amino]-5-methyl-6-oxidanylidene-4~{H}-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate / Ro-15-4513 / アンタゴニスト*YM / Ro15-4513
由来	homo sapiens (ヒト) lama glama (ラマ)
キーワード	MEMBRANE PROTEIN (膜タンパク質) / pentameric ligand-gated ion channel / neurotransmitter receptor (神経伝達物質受容体) / GABA receptor (GABA受容体)