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Updated: Jun 13, 2025

Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
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Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels

Published on: May 18, 2009

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Insights into lysophosphatidylserine recognition and Gα12/13-coupling specificity of P2Y10

Han Yin1, Nozomi Kamakura2, Yu Qian1

  • 1Laboratory of Receptor Structure and Signaling, HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China.

Cell Chemical Biology
|September 12, 2024
PubMed

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.

Keywords:
Gα(12/13) couplingGα(13) coupling selectivityP2Y10lysophosphatidylserinelysophosphatidylserine receptor

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