9WIK

Cryo-EM structure of GPR84-Gi complex with DL-175

これはPDB形式変換不可エントリーです。

9WIK の概要

• エントリーDOI: 10.2210/pdb9wik/pdb
• EMDBエントリー: 65999
• 分子名称: Guanine nucleotide-binding protein G(i) subunit alpha-1, 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, signaling protein, 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: 193418.04

構造登録者

Suzuki, S.,Nishikawa, K.,Tran, D.P.,Akio, K.,Fujiyoshi, Y. (登録日: 2025-08-28, 公開日: 2026-07-01, 最終更新日: 2026-07-29)

主引用文献

Suzuki, S.,Tran, D.P.,Nishikawa, K.,Kitao, A.,Fujiyoshi, Y.
Mechanistic insight into signal bias by the agonist-dependent conformational dynamics of GPR84.
Nat Commun, 2026

PubMed Abstract: GPR84 is an orphan class A GPCR primarily expressed in immune cells, where it plays key roles in inflammation and metabolism. Here, we present the cryo-electron microscopy structures of the GPR84-Gi complex bound to the G protein-biased agonist DL-175, and the inactive state of GPR84 bound to the antagonist GLPG1205. Combined with signaling assays and molecular dynamics simulations, these structures elucidate the conformational landscape spanning the inactive and G protein-biased active states of GPR84, providing a mechanistic basis for biased agonism. Notably, steric interactions between DL-175 and L336 selectively preclude the conformational changes required for efficient β-arrestin recruitment without compromising G protein activation. These structural insights provide a structural context for the rational design of GPR84-targeted therapeutics with precisely tuned signaling profiles.

PubMed: 42463693
DOI: 10.1038/s41467-026-75728-9

実験手法

ELECTRON MICROSCOPY (3.3 Å)