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	A single allosteric site merges activation, modulation and inhibition in TRPM5.
ジャーナル・号・ページ	Nat Chem Biol, Vol. 22, Issue 3, Page 402-410, Year 2026
掲載日	2026年1月5日
著者	Zheng Ruan / Junuk Lee / Yangyang Li / Ian J Orozco / Juan Du / Wei Lü /
PubMed 要旨	TRPM5 is a Ca-activated monovalent cation channel essential for taste perception, insulin secretion and gastrointestinal chemosensation. Canonical TRPM5 activation requires Ca binding at two distinct ...TRPM5 is a Ca-activated monovalent cation channel essential for taste perception, insulin secretion and gastrointestinal chemosensation. Canonical TRPM5 activation requires Ca binding at two distinct sites: an agonist site within the lower vestibule of the S1-S4 pocket in the transmembrane domain (Ca) and a modulatory site in the intracellular domain (Ca) that tunes voltage dependence and agonist sensitivity. Here we characterize CBTA as a noncalcium agonist that binds to the upper vestibule of the S1-S4 pocket, directly above Ca. CBTA alone mimics the dual role of Ca and Ca, merging agonist activation with voltage modulation. CBTA also renders TRPM5 supersensitive to Ca, synergistically hyperactivating the channel even at near-resting Ca levels. We further demonstrate that the inhibitor triphenylphosphine oxide binds the same site but stabilizes a nonconductive state. These opposing effects reveal the upper S1-S4 pocket as a multifunctional regulatory hub integrating activation, inhibition and modulation in TRPM5.
リンク	Nat Chem Biol / PubMed:41491833 / PubMed Central
手法	EM (単粒子)
解像度	2.75 - 3.5 Å
構造データ	EMDB-71244: The consensus map of zebrafish TRPM5 with 1mM EDTA and 0.5mM CBTA 手法: EM (単粒子) / 解像度: 3.1 Å 71245 9p3n EMDB-71245, PDB-9p3n: The open state of zebrafish TRPM5 with 1mM EDTA and 0.5mM CBTA 手法: EM (単粒子) / 解像度: 3.5 Å 71246 9p3o EMDB-71246, PDB-9p3o: Zebrafish TRPM5 with 5mM calcium and 0.5mM CBTA 手法: EM (単粒子) / 解像度: 2.92 Å EMDB-71247: Zebrafish TRPM5 with 0.2mM calcium 手法: EM (単粒子) / 解像度: 2.9 Å EMDB-71248: Zebrafish TRPM5 with 1uM calcium 手法: EM (単粒子) / 解像度: 3.24 Å EMDB-71249: Zebrafish TRPM5 with 2uM Ca in GDN detergent 手法: EM (単粒子) / 解像度: 3.3 Å 71250 9p3p EMDB-71250, PDB-9p3p: Zebrafish TRPM5 with 5mM EGTA and 0.5mM CBTA 手法: EM (単粒子) / 解像度: 3.0 Å 71251 9p3q EMDB-71251, PDB-9p3q: Zebrafish TRPM5 D797A mutant with 5mM calcium 手法: EM (単粒子) / 解像度: 3.5 Å 71252 9p3r EMDB-71252, PDB-9p3r: Zebrafish TRPM5 D797A mutant with 5mM calcium and 0.5mM CBTA 手法: EM (単粒子) / 解像度: 3.5 Å 71253 9p3s EMDB-71253, PDB-9p3s: Zebrafish TRPM5 D797N mutant with 5mM calcium and 0.5mM CBTA 手法: EM (単粒子) / 解像度: 3.27 Å 71254 9p3t EMDB-71254, PDB-9p3t: Zebrafish TRPM5 with 5mM calcium and 0.5mM TPPO 手法: EM (単粒子) / 解像度: 3.0 Å 71255 9p3u EMDB-71255, PDB-9p3u: Zebrafish TRPM5 E337A mutant with 5mM calcium and 0.5mM CBTA 手法: EM (単粒子) / 解像度: 2.75 Å 71256 9p3v EMDB-71256, PDB-9p3v: Zebrafish TRPM5 Q771A mutant with 5mM calcium and 0.5mM CBTA 手法: EM (単粒子) / 解像度: 2.75 Å 71257 9p3w EMDB-71257, PDB-9p3w: Zebrafish TRPM5 Q771A mutant with 5mM calcium 手法: EM (単粒子) / 解像度: 2.85 Å
化合物	ChemComp-CA: Unknown entry / カルシウムジカチオン ChemComp-YUY: (2R)-2-(hydroxymethyl)-4-{[(25R)-10alpha,14beta,17beta-spirost-5-en-3beta-yl]oxy}butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside ChemComp-YUV: (25R)-14beta,17beta-spirost-5-en-3beta-ol / ジオスゲニン PDB-1cgw: SITE DIRECTED MUTATIONS OF THE ACTIVE SITE RESIDUE TYROSINE 195 OF CYCLODEXTRIN GLYCOSYLTRANSFERASE FROM BACILLUS CIRCULANS STRAIN 251 AFFECTING ACTIVITY AND PRODUCT SPECIFICITY ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン PDB-1cgz: CHALCONE SYNTHASE FROM ALFALFA COMPLEXED WITH RESVERATROL PDB-1cg0: STRUCTURE OF ADENYLOSUCCINATE SYNTHETASE FROM E. COLI COMPLEXED WITH HADACIDIN, GDP, 6-PHOSPHORYL-IMP, AND MG2+ PDB-1cg5: DEOXY FORM HEMOGLOBIN FROM DASYATIS AKAJEI ChemComp-HOH: WATER
由来	danio rerio (ゼブラフィッシュ)
キーワード	TRANSPORT PROTEIN / TRPM5 channel; ion channel; cation channel; sodium channel; calcium; CBTA / TRPM5 channel / ion channel / cation channel / sodium channel / TRANSFERASE