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	Bitter taste TAS2R14 activation by intracellular tastants and cholesterol.
ジャーナル・号・ページ	Nature, Year 2024
掲載日	2024年5月22日
著者	Xiaolong Hu / Weizhen Ao / Mingxin Gao / Lijie Wu / Yuan Pei / Shenhui Liu / Yiran Wu / Fei Zhao / Qianqian Sun / Junlin Liu / Longquan Jiang / Xin Wang / Yan Li / Qiwen Tan / Jie Cheng / Fan Yang / Chi Yang / Jinpeng Sun / Tian Hua / Zhi-Jie Liu /
PubMed 要旨	Bitter taste receptors, particularly TAS2R14, play central roles in discerning a wide array of bitter substances, ranging from dietary components to pharmaceutical agents. TAS2R14 is also widely ...Bitter taste receptors, particularly TAS2R14, play central roles in discerning a wide array of bitter substances, ranging from dietary components to pharmaceutical agents. TAS2R14 is also widely expressed in extragustatory tissues, suggesting its extra roles in diverse physiological processes and potential therapeutic applications. Here we present cryogenic electron microscopy structures of TAS2R14 in complex with aristolochic acid, flufenamic acid and compound 28.1, coupling with different G-protein subtypes. Uniquely, a cholesterol molecule is observed occupying what is typically an orthosteric site in class A G-protein-coupled receptors. The three potent agonists bind, individually, to the intracellular pockets, suggesting a distinct activation mechanism for this receptor. Comprehensive structural analysis, combined with mutagenesis and molecular dynamic simulation studies, elucidate the broad-spectrum ligand recognition and activation of the receptor by means of intricate multiple ligand-binding sites. Our study also uncovers the specific coupling modes of TAS2R14 with gustducin and G proteins. These findings should be instrumental in advancing knowledge of bitter taste perception and its broader implications in sensory biology and drug discovery.
リンク	Nature / PubMed:38776963
手法	EM (単粒子)
解像度	2.77 - 3.3 Å
構造データ	38580 EMDBエントリ画像なし 8xql EMDB-38580, PDB-8xql: Structure of human class T GPCR TAS2R14-miniGs/gust complex with Aristolochic acid A. 手法: EM (単粒子) / 解像度: 2.99 Å 38582 EMDBエントリ画像なし 8xqn EMDB-38582, PDB-8xqn: Structure of human class T GPCR TAS2R14-DNGi complex with Aristolochic acid A. 手法: EM (単粒子) / 解像度: 3.05 Å 38583 EMDBエントリ画像なし 8xqo EMDB-38583, PDB-8xqo: Structure of human class T GPCR TAS2R14-Gi complex with Aristolochic acid A. 手法: EM (単粒子) / 解像度: 2.77 Å 38584 EMDBエントリ画像なし 8xqp EMDB-38584, PDB-8xqp: Structure of human class T GPCR TAS2R14-Gustducin complex with Aristolochic acid A. 手法: EM (単粒子) / 解像度: 3.29 Å 38586 EMDBエントリ画像なし 8xqr EMDB-38586, PDB-8xqr: Structure 2 of human class T GPCR TAS2R14-miniGs/gust complex with Flufenamic acid. 手法: EM (単粒子) / 解像度: 3.2 Å 38587 EMDBエントリ画像なし 8xqs EMDB-38587, PDB-8xqs: Structure of human class T GPCR TAS2R14-DNGi complex with Flufenamic acid. 手法: EM (単粒子) / 解像度: 3.3 Å 38588 EMDBエントリ画像なし 8xqt EMDB-38588, PDB-8xqt: Structure of human class T GPCR TAS2R14-Gi complex. 手法: EM (単粒子) / 解像度: 2.94 Å 39376 EMDBエントリ画像なし 8yky EMDB-39376, PDB-8yky: Structure of human class T GPCR TAS2R14-Ggustducin complex with agonist 28.1 手法: EM (単粒子) / 解像度: 2.99 Å
化合物	ChemComp-GOQ: 8-methoxy-6-nitro-naphtho[1,2-e][1,3]benzodioxole-5-carboxylic acid ChemComp-CLR: CHOLESTEROL / コレステロ-ル ChemComp-FLF: 2-[[3-(TRIFLUOROMETHYL)PHENYL]AMINO] BENZOIC ACID / フルフェナム酸 / 抗炎症剤, 阻害剤YM PDB-1aei*: CRYSTAL STRUCTURE OF THE ANNEXIN XII HEXAMER
由来	homo sapiens (ヒト) synthetic construct (人工物) clostridium perfringens (ウェルシュ菌)
キーワード	SIGNALING PROTEIN / GPCR / Tas2R14 / miniGsg / GOQ / DNGi / Bitter receptor / Gi / Bitter Receptor. / Gustducin / GPCR Tas2R14 miniGsg FLF Bitter receptor / FLF / Ggustducin / 28.1 / TASTE RECEPTOR.