8IHB

Cryo-EM structure of HCA2-Gi complex with GSK256073

8IHB の概要

• エントリーDOI: 10.2210/pdb8ihb/pdb
• EMDBエントリー: 35442
• 分子名称: Soluble cytochrome b562,Hydroxycarboxylic acid receptor 2, Guanine nucleotide-binding protein G(i) subunit alpha-1, scFv16, ... (7 entities in total)
• 機能のキーワード: gpcr, signaling protein
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 191701.55

構造登録者

Suzuki, S.,Nishikawa, K.,Suzuki, H.,Fujiyoshi, Y. (登録日: 2023-02-22, 公開日: 2023-09-13, 最終更新日: 2025-06-18)

主引用文献

Suzuki, S.,Tanaka, K.,Nishikawa, K.,Suzuki, H.,Oshima, A.,Fujiyoshi, Y.
Structural basis of hydroxycarboxylic acid receptor signaling mechanisms through ligand binding.
Nat Commun, 14:5899-5899, 2023

PubMed Abstract: Hydroxycarboxylic acid receptors (HCA) are expressed in various tissues and immune cells. HCA2 and its agonist are thus important targets for treating inflammatory and metabolic disorders. Only limited information is available, however, on the active-state binding of HCAs with agonists. Here, we present cryo-EM structures of human HCA2-Gi and HCA3-Gi signaling complexes binding with multiple compounds bound. Agonists were revealed to form a salt bridge with arginine, which is conserved in the HCA family, to activate these receptors. Extracellular regions of the receptors form a lid-like structure that covers the ligand-binding pocket. Although transmembrane (TM) 6 in HCAs undergoes dynamic conformational changes, ligands do not directly interact with amino acids in TM6, suggesting that indirect signaling induces a slight shift in TM6 to activate Gi proteins. Structural analyses of agonist-bound HCA2 and HCA3 together with mutagenesis and molecular dynamics simulation provide molecular insights into HCA ligand recognition and activation mechanisms.

PubMed: 37736747
DOI: 10.1038/s41467-023-41650-7

実験手法

ELECTRON MICROSCOPY (2.85 Å)