8IQ6

Cryo-EM structure of Latanoprost-bound prostaglandin-F2-alpha receptor-miniGq-Nb35 complex

8IQ6 の概要

• エントリーDOI: 10.2210/pdb8iq6/pdb
• EMDBエントリー: 35658
• 分子名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• 機能のキーワード: gpcr, complex, prostaglandin receptor, agonist, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 133434.36

構造登録者

Lv, X.,Gao, K.,Nie, J.,Zhang, X.,Zhang, S.,Ren, Y.,Li, Q.,Huang, J.,Liu, L.,Zhang, X.,Sun, X.,Zhang, W.,Liu, X. (登録日: 2023-03-15, 公開日: 2024-01-31, 最終更新日: 2024-11-06)

主引用文献

Lv, X.,Gao, K.,Nie, J.,Zhang, X.,Zhang, S.,Ren, Y.,Sun, X.,Li, Q.,Huang, J.,Liu, L.,Zhang, X.,Zhang, W.,Liu, X.
Structures of human prostaglandin F 2 alpha receptor reveal the mechanism of ligand and G protein selectivity.
Nat Commun, 14:8136-8136, 2023

PubMed Abstract: 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.

PubMed: 38065938
DOI: 10.1038/s41467-023-43922-8

実験手法

ELECTRON MICROSCOPY (3.4 Å)