8KGG

LPS-bound P2Y10 in complex with G13

8KGG の概要

• エントリーDOI: 10.2210/pdb8kgg/pdb
• EMDBエントリー: 37220
• 分子名称: Guanine nucleotide-binding protein G(i) subunit alpha-2,Guanine nucleotide-binding protein subunit alpha-13, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, scFv16, ... (6 entities in total)
• 機能のキーワード: gpcr-g-protein complex, 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: 137937.84

構造登録者

He, Y.,Yin, Y. (登録日: 2023-08-19, 公開日: 2024-07-31, 最終更新日: 2024-12-04)

主引用文献

Yin, H.,Kamakura, N.,Qian, Y.,Tatsumi, M.,Ikuta, T.,Liang, J.,Xu, Z.,Xia, R.,Zhang, A.,Guo, C.,Inoue, A.,He, Y.
Insights into lysophosphatidylserine recognition and G alpha 12/13 -coupling specificity of P2Y10.
Cell Chem Biol, 31:1899-1908.e5, 2024

PubMed Abstract: The lysophosphatidylserine (LysoPS) receptor P2Y10, also known as LPS, plays crucial roles in the regulation of immune responses and holds promise for the treatment of autoimmune diseases. Here, we report the cryoelectron microscopy (cryo-EM) structure of LysoPS-bound P2Y10 in complex with an engineered G heterotrimeric protein. The structure and a mutagenesis study highlight the predominant role of a comprehensive polar network in facilitating the binding and activation of the receptor by LysoPS. This interaction pattern is preserved in GPR174, but not in GPR34. Moreover, our structural study unveils the essential interactions that underlie the Gα engagement of P2Y10 and identifies key determinants for Gα-vs.-Gα-coupling selectivity, whose mutations selectively disrupt Gα engagement while preserving the intact coupling of Gα. The combined structural and functional studies provide insights into the molecular mechanisms of LysoPS recognition and Gα coupling specificity.

PubMed: 39265572
DOI: 10.1016/j.chembiol.2024.08.005

実験手法

ELECTRON MICROSCOPY (3.06 Å)