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	(-)-Englerin A binding to human TRPC5 exposes an aromatic interaction network in channel activation.
ジャーナル・号・ページ	Nat Commun, Vol. 17, Issue 1, Year 2026
掲載日	2026年4月29日
著者	Sebastian A Porav / Alexandra Ptakova / Claudia C Bauer / Kasia L R Hammond / David J Beech / Viktorie Vlachova / Stephen P Muench / Robin S Bon /
PubMed 要旨	TRPC4/5 cation channels are polymodal cellular sensors and emerging drug targets in various human pathologies. The plant natural product (-)-englerin A (EA) is a potent, selective TRPC4/5 agonist ...TRPC4/5 cation channels are polymodal cellular sensors and emerging drug targets in various human pathologies. The plant natural product (-)-englerin A (EA) is a potent, selective TRPC4/5 agonist that has transformed TRPC4/5 research. However, the structural basis of EA-mediated TRPC4/5 activation has remained elusive, limiting our ability to understand and exploit EA's pharmacology. Here, we present nine high-resolution cryo-EM structures of human TRPC5, representing different states and ligand occupancies, which show that EA occupies a conserved lipid binding site between channel subunits. Conformational changes of residues surrounding this binding site - most notably in the aromatic interaction network around Phe520 - result in rearrangement of the pore helices into a pre-open state. Our structural models are consistent with the effects of mutagenesis on EA's potency, efficacy and activation kinetics, and allow us to rationalise competitive inhibition by other TRPC4/5 modulators as well as EA's selectivity profile within the TRPC family. Our structural insights into the mode-of-action of a widely used TRPC4/5 agonist will underpin fundamental TRPC4/5 research and ongoing drug discovery programmes.
リンク	Nat Commun / PubMed:42056091 / PubMed Central
手法	EM (単粒子)
解像度	2.3 - 3.2 Å
構造データ	54186 9rrf EMDB-54186, PDB-9rrf: TRPC5 apo cryoEM map in the presence of pluronic acid (PA), state 2 手法: EM (単粒子) / 解像度: 2.3 Å 54187 9rrm EMDB-54187, PDB-9rrm: Human TRPC5 in complex with (-) englerin A, full occupancy, state 1, on 290 nm gold foil holes (HexAuFoil) 手法: EM (単粒子) / 解像度: 2.5 Å 54188 9rrn EMDB-54188, PDB-9rrn: Human TRPC5 in complex with (-) englerin A, full occupancy, state 2, on 290 nm gold foil holes (HexAuFoil) 手法: EM (単粒子) / 解像度: 2.5 Å 54189 9rro EMDB-54189, PDB-9rro: Human TRPC5 in complex with (-) englerin A, full occupancy, intermediary desensitized state 手法: EM (単粒子) / 解像度: 2.8 Å 54193 9rrq EMDB-54193, PDB-9rrq: Human TRPC5 in complex with (-) englerin A, partial occupancy (2EA:2LIP stoichiometry) state 1 手法: EM (単粒子) / 解像度: 2.9 Å 54204 9rru EMDB-54204, PDB-9rru: Human TRPC5 in complex with (-) englerin A, mixed occupancy, state 1 手法: EM (単粒子) / 解像度: 3.2 Å 54218 9rsg EMDB-54218, PDB-9rsg: Human TRPC5 in complex with (-) englerin A, mixed occupancy_2, state 2 手法: EM (単粒子) / 解像度: 3.2 Å 54219 9rsh EMDB-54219, PDB-9rsh: Human TRPC5 in complex with (-) englerin A, mixed occupancy, state 2 手法: EM (単粒子) / 解像度: 3.0 Å 54291 9rvv EMDB-54291, PDB-9rvv: Human TRPC5 in complex with (-) englerin A, partial occupancy (2EA:2LIP stoichiometry) state 2 手法: EM (単粒子) / 解像度: 3.0 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-YZY: (2S)-2-(hexadecanoyloxy)-3-hydroxypropyl (9Z)-octadec-9-enoate ChemComp-PTY: PHOSPHATIDYLETHANOLAMINE / リン脂質YM ChemComp-Y01: CHOLESTEROL HEMISUCCINATE ChemComp-CA: Unknown entry PDB-1l55*: ANALYSIS OF THE INTERACTION BETWEEN CHARGED SIDE CHAINS AND THE ALPHA-HELIX DIPOLE USING DESIGNED THERMOSTABLE MUTANTS OF PHAGE T4 LYSOZYME
由来	homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN / Ion Channel / apo / TRPC5 / (-) englerin A / agonist