9EE5

Cryo-EM structure of the ONO2550289-bound prostaglandin D2 receptor (DP1)-bRIL-Fab complex

これはPDB形式変換不可エントリーです。

9EE5 の概要

• エントリーDOI: 10.2210/pdb9ee5/pdb
• EMDBエントリー: 47950
• 分子名称: anti-BRIL Fab Heavy Chain, anti-Fab Nanobody synthetic construct, anti-BRIL Fab Light Chain, ... (5 entities in total)
• 機能のキーワード: gpcr, cryo-em, dp1, inverse agonist, ono2550289, prostaglandin d2 receptor, prostanoid dp receptor, pgd receptor, ptgdr, dp1-bril chimera, membrane protein, membrane protein-immune system complex, membrane protein/immune system
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 117248.55

構造登録者

Davoudinasab, B.,Cherezov, V.,Han, G.W. (登録日: 2024-11-18, 公開日: 2025-09-03, 最終更新日: 2025-10-22)

主引用文献

Davoudinasab, B.,Raskovalov, A.,Lee, W.,Kim, D.,Kim, H.,Lam, J.H.,Han, G.W.,Katritch, V.,Cherezov, V.
Structural insights into the mechanism of activation and inhibition of the prostaglandin D2 receptor 1.
Nat Commun, 16:8944-8944, 2025

PubMed Abstract: The prostaglandin D2 receptor 1 (DP1), a member of the prostanoid G protein-coupled receptor (GPCR) family, plays critical roles in allergic responses, sleep regulation, immune modulation, and vasodilation. Here, we present five high-resolution cryo-electron microscopy (cryo-EM) structures of the human DP1 receptor, including an apo structure, two inactive state structures bound to two different inverse agonists developed by ONO Pharmaceutical, and two active state structures in complex with the G protein and bound to the endogenous agonist PGD2 and its selective derivative BW245C. Structural analysis, complemented by molecular dynamics simulations and site-directed mutagenesis, reveals key residues involved in ligand recognition and suggests a distinct activation mechanism for DP1, which lacks most of the conserved class A GPCR motifs. Notably, the unique residue K76 within the conserved sodium pocket acts as a major activation switch, while amphiphilic helix 8 adopts an unconventional orientation essential for receptor function. These findings offer valuable insights into the structure and function of prostanoid receptors and may facilitate the development of therapeutics targeting DP1.

PubMed: 41062467
DOI: 10.1038/s41467-025-64002-z

実験手法

ELECTRON MICROSCOPY (2.89 Å)