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	Sterol derivative binding to the orthosteric site causes conformational changes in an invertebrate Cys-loop receptor.
ジャーナル・号・ページ	Elife, Vol. 12, Year 2023
掲載日	2023年7月3日
著者	Steven De Gieter / Casey I Gallagher / Eveline Wijckmans / Diletta Pasini / Chris Ulens / Rouslan G Efremov /
PubMed 要旨	Cys-loop receptors or pentameric ligand-gated ion channels are mediators of electrochemical signaling throughout the animal kingdom. Because of their critical function in neurotransmission and high ...Cys-loop receptors or pentameric ligand-gated ion channels are mediators of electrochemical signaling throughout the animal kingdom. Because of their critical function in neurotransmission and high potential as drug targets, Cys-loop receptors from humans and closely related organisms have been thoroughly investigated, whereas molecular mechanisms of neurotransmission in invertebrates are less understood. When compared with vertebrates, the invertebrate genomes underwent a drastic expansion in the number of the nACh-like genes associated with receptors of unknown function. Understanding this diversity contributes to better insight into the evolution and possible functional divergence of these receptors. In this work, we studied orphan receptor Alpo4 from an extreme thermophile worm . Sequence analysis points towards its remote relation to characterized nACh receptors. We solved the cryo-EM structure of the lophotrochozoan nACh-like receptor in which a CHAPS molecule is tightly bound to the orthosteric site. We show that the binding of CHAPS leads to extending of the loop C at the orthosteric site and a quaternary twist between extracellular and transmembrane domains. Both the ligand binding site and the channel pore reveal unique features. These include a conserved Trp residue in loop B of the ligand binding site which is flipped into an apparent self-liganded state in the apo structure. The ion pore of Alpo4 is tightly constricted by a ring of methionines near the extracellular entryway of the channel pore. Our data provide a structural basis for a functional understanding of Alpo4 and hints towards new strategies for designing specific channel modulators.
リンク	Elife / PubMed:37395731 / PubMed Central
手法	EM (単粒子)
解像度	3.4 - 6.2 Å
構造データ	16308 8bx5 EMDB-16308, PDB-8bx5: Alvinella pompejana nicotinic acetylcholine receptor Alpo4 in apo state (dataset 1) 手法: EM (単粒子) / 解像度: 4.2 Å 16314 8bxb EMDB-16314, PDB-8bxb: Alvinella pompejana nicotinic acetylcholine receptor Alpo in apo state (dataset 2) 手法: EM (単粒子) / 解像度: 3.9 Å 16315 8bxd EMDB-16315, PDB-8bxd: Alvinella pompejana nicotinic acetylcholine receptor Alpo4 in apo state (Alpo4_LMNG_Serotonin dataset 4) 手法: EM (単粒子) / 解像度: 6.2 Å 16316 8bxe EMDB-16316, PDB-8bxe: Alvinella pompejana nicotinic acetylcholine receptor Alpo4 in apo state (Alpo4_comb dataset 3) 手法: EM (単粒子) / 解像度: 3.9 Å 16317 8bxf EMDB-16317, PDB-8bxf: Alvinella pompejana nicotinic acetylcholine receptor Alpo4 in apo state (Alpo4_apo, dataset 1) 手法: EM (単粒子) / 解像度: 3.4 Å 16326 8byi EMDB-16326, PDB-8byi: Alvinella pompejana nicotinic acetylcholine receptor Alpo4 in complex with CHAPS(Alpo4_CHAPS) 手法: EM (単粒子) / 解像度: 4.1 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 ChemComp-HOH: WATER ChemComp-CPS: 3-[(3-CHOLAMIDOPROPYL)DIMETHYLAMMONIO]-1-PROPANESULFONATE / 可溶化剤YM ChemComp-NA*: Unknown entry / ナトリウムカチオン
由来	alvinella pompejana (無脊椎動物)
キーワード	MEMBRANE PROTEIN / Cys-loop receptor / pentameric ligand-gated ion channel / Alpo / nAChR