8KGG

LPS-bound P2Y10 in complex with G13

Summary for 8KGG

• Entry DOI: 10.2210/pdb8kgg/pdb
• EMDB information: 37220
• Descriptor: 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)
• Functional Keywords: gpcr-g-protein complex, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 137937.84

Authors

He, Y.,Yin, Y. (deposition date: 2023-08-19, release date: 2024-07-31, Last modification date: 2024-11-13)

Primary citation

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, 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

Experimental method

ELECTRON MICROSCOPY (3.06 Å)