8ZW0

Cryo-EM strcuture of Prostaglandin D2 Receptor DP1 activated by PGD2

8ZW0 の概要

• エントリーDOI: 10.2210/pdb8zw0/pdb
• EMDBエントリー: 60514
• 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, Soluble cytochrome b562,Prostaglandin D2 receptor, ... (7 entities in total)
• 機能のキーワード: prostaglandin, dp1, pgd2, 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: 161583.79

構造登録者

Xu, J.,Xu, Y.,Wu, C.,Xu, H.E. (登録日: 2024-06-12, 公開日: 2025-05-28, 最終更新日: 2025-06-25)

主引用文献

Xu, J.,Wu, Y.,Xu, Y.,Li, Y.,He, X.,Zhang, H.,Wang, J.J.,Hou, J.,Li, J.,Hu, W.,Wu, K.,Yuan, Q.,Wu, C.,Xu, H.E.
Molecular basis for ligand recognition and receptor activation of the prostaglandin D2 receptor DP1.
Proc.Natl.Acad.Sci.USA, 122:e2501902122-e2501902122, 2025

PubMed Abstract: The prostaglandin D2 receptor 1 (DP1), a rhodopsin-like Class A GPCR, orchestrates critical physiological and pathological processes, ranging from sleep regulation to inflammatory responses and cardiovascular function. Despite its therapeutic significance, structural insights into DP1 activation mechanisms have remained elusive. Here, using cryoelectron microscopy (cryo-EM), we determined high-resolution structures of human DP1 in both inactive and active states, with the latter captured in complex with its endogenous agonist PGD2 or the synthetic agonist BW245C, bound to the stimulatory G protein, Gs. Our structures, coupled with functional and mutagenesis studies, unveiled unique structural features of DP1, including an alternative activation mechanism, ligand-selectivity determinants, and G protein coupling characteristics. These molecular insights provide a rational framework for designing selective DP1-targeted therapeutics, both agonists and antagonists, with enhanced specificity and reduced off-target effects, opening broad avenues for treating DP1-associated disorders.

PubMed: 40440061
DOI: 10.1073/pnas.2501902122

実験手法

ELECTRON MICROSCOPY (2.72 Å)