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	Structural and dynamic insights into agonist recognition and function of the thromboxane A receptor.
ジャーナル・号・ページ	Nat Commun, Vol. 17, Issue 1, Year 2026
掲載日	2026年2月23日
著者	Pawel Krawinski / Donna Matzov / Aoife Ryder / Kanhaya Lal / Dmitry S Karlov / Georges Chalhoub / Eamon P Mulvaney / B Therese Kinsella / Peter J McCormick / Martin Caffrey / Irina G Tikhonova / Moran Shalev-Benami /
PubMed 要旨	The thromboxane A receptor (TP), expressed in platelets and smooth muscle, plays an important role in blood clotting and muscle contraction. The endogenous ligand of this G protein-coupled receptor ...The thromboxane A receptor (TP), expressed in platelets and smooth muscle, plays an important role in blood clotting and muscle contraction. The endogenous ligand of this G protein-coupled receptor (GPCR), thromboxane A (TXA), is a short-lived arachidonic acid metabolite with a half-life of ∼30 seconds, which makes investigating the TP structure and activation mechanism highly challenging. Here we determine the structures of the TP in complex with the synthetic agonists, U46619 and I-BOP, stable analogues of the natural ligand, in the presence of the signalling protein partner, G. The structures reveal a unique activation switch for the receptor that differs from typical class A GPCR family members. Complemented by functional studies, mutational analysis, docking, and molecular dynamics (MD) simulations, our investigation highlights the differences between agonist and antagonist binding and explores the ligand entry mechanism to the binding pocket from within the membrane via a molecular gate composed of two transmembrane helices. In addition, our study provides crucial information to aid in the rational design of compounds targeting the TP, and offers mechanistic insights into inherited disorders associated with mutations in the TP.
リンク	Nat Commun / PubMed:41730883 / PubMed Central
手法	EM (単粒子)
解像度	3.22 - 3.52 Å
構造データ	51324 9gg5 EMDB-51324, PDB-9gg5: Cryo-EM structure of Thromboxane A2 receptor-miniGq protein complex bound to U46619 手法: EM (単粒子) / 解像度: 3.26 Å 51331 9ggg EMDB-51331, PDB-9ggg: Cryo-EM structure of Thromboxane A2 receptor-miniGq Protein Complex bound to I-BOP 手法: EM (単粒子) / 解像度: 3.25 Å EMDB-51332: Consensus cryo-EM map of Thromboxane A2 receptor-Gq Protein Complex bound to U46619 手法: EM (単粒子) / 解像度: 3.26 Å EMDB-51341: Cryo-EM map of Thromboxane A2 receptor-Gq Protein Complex bound to U46619 focused refined on the receptor 手法: EM (単粒子) / 解像度: 3.26 Å EMDB-51342: Cryo-EM map of Thromboxane A2 receptor-Gq Protein Complex bound to U46619 focused refined on the G proteins 手法: EM (単粒子) / 解像度: 3.26 Å EMDB-51343: Cryo-EM map of Thromboxane A2 receptor-Gq Protein Complex bound to IBOP 手法: EM (単粒子) / 解像度: 3.25 Å EMDB-51344: Cryo-EM map of Thromboxane A2 receptor-Gq Protein Complex bound to I-BOP focused refined on the receptor 手法: EM (単粒子) / 解像度: 3.52 Å EMDB-51345: Cryo-EM map of Thromboxane A2 receptor-Gq Protein Complex bound to I-BOP focused refined on the G proteins 手法: EM (単粒子) / 解像度: 3.22 Å
化合物	ChemComp-PUC: (5Z)-7-{(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-2-oxabicyclo[2.2.1]hept-5-yl}hept-5-enoic acid / U-46619 ChemComp-CLR: CHOLESTEROL / コレステロ-ル PDB-1ik0: Solution Structure of Human IL-13
由来	homo sapiens (ヒト) synthetic construct (人工物)
キーワード	MEMBRANE PROTEIN / Single particle cryo-EM / GPCR / G-proteins