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-Structure paper
タイトル | Structures of human prostaglandin F receptor reveal the mechanism of ligand and G protein selectivity. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 8136, Year 2023 |
掲載日 | 2023年12月8日 |
著者 | Xiuqing Lv / Kaixuan Gao / Jia Nie / Xin Zhang / Shuhao Zhang / Yinhang Ren / Xiaoou Sun / Qi Li / Jingrui Huang / Lijuan Liu / Xiaowen Zhang / Weishe Zhang / Xiangyu Liu / |
PubMed 要旨 | Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is ...Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is clinically used to treat postpartum hemorrhage (PPH). However, off-target activation of closely related receptors such as the prostaglandin E receptor subtype EP3 (EP3 receptor) by carboprost results in side effects and limits the clinical application. Meanwhile, the FP receptor selective agonist latanoprost is not suitable to treat PPH due to its poor solubility and fast clearance. Here, we present two cryo-EM structures of the FP receptor bound to carboprost and latanoprost-FA (the free acid form of latanoprost) at 2.7 Å and 3.2 Å resolution, respectively. The structures reveal the molecular mechanism of FP receptor selectivity for both endogenous prostaglandins and clinical drugs, as well as the molecular mechanism of G protein coupling preference by the prostaglandin receptors. The structural information may guide the development of better prostaglandin drugs. |
リンク | Nat Commun / PubMed:38065938 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.7 - 3.4 Å |
構造データ | EMDB-35657, PDB-8iq4: EMDB-35658, PDB-8iq6: |
化合物 | ChemComp-87Q: ChemComp-7WT: |
由来 |
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キーワード | MEMBRANE PROTEIN / GPCR / Complex / Prostaglandin receptor / Agonist |