EMD-37220
LPS-bound P2Y10 in complex with G13
EMD-37220
Single-particle3.06 Å
![EMD-37220](https://www.ebi.ac.uk/emdb/images/entry/EMD-37220/400_37220.gif)
Map released: 31/07/2024
Last modified: 04/12/2024
Sample Organism:
Homo sapiens
Sample: GPCR/G-protein complex
Fitted models: 8kgg (Avg. Q-score: 0.518)
Deposition Authors: He Y, Yin Y
Sample: GPCR/G-protein complex
Fitted models: 8kgg (Avg. Q-score: 0.518)
Deposition Authors: He Y, Yin Y
Insights into lysophosphatidylserine recognition and G alpha 12/13 -coupling specificity of P2Y10.
Yin H,
Kamakura N,
Qian Y,
Tatsumi M,
Ikuta T,
Liang J,
Xu Z,
Xia R,
Zhang A,
Guo C,
Inoue A,
He Y
(2024) Cell Chem Biol , 31 , 1899 - 1908.e5
(2024) Cell Chem Biol , 31 , 1899 - 1908.e5
Abstract:
The lysophosphatidylserine (LysoPS) receptor P2Y10, also known as LPS2, 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 G13 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 Gα13 engagement of P2Y10 and identifies key determinants for Gα12-vs.-Gα13-coupling selectivity, whose mutations selectively disrupt Gα12 engagement while preserving the intact coupling of Gα13. The combined structural and functional studies provide insights into the molecular mechanisms of LysoPS recognition and Gα12/13 coupling specificity.
The lysophosphatidylserine (LysoPS) receptor P2Y10, also known as LPS2, 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 G13 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 Gα13 engagement of P2Y10 and identifies key determinants for Gα12-vs.-Gα13-coupling selectivity, whose mutations selectively disrupt Gα12 engagement while preserving the intact coupling of Gα13. The combined structural and functional studies provide insights into the molecular mechanisms of LysoPS recognition and Gα12/13 coupling specificity.