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TitleInsights into lysophosphatidylserine recognition and Gα-coupling specificity of P2Y10.
Journal, issue, pagesCell Chem Biol, Vol. 31, Issue 11, Page 1899-11908.e5, Year 2024
Publish dateNov 21, 2024
AuthorsHan Yin / Nozomi Kamakura / Yu Qian / Manae Tatsumi / Tatsuya Ikuta / Jiale Liang / Zhenmei Xu / Ruixue Xia / Anqi Zhang / Changyou Guo / Asuka Inoue / Yuanzheng He /
PubMed AbstractThe 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 ...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.
External linksCell Chem Biol / PubMed:39265572
MethodsEM (single particle)
Resolution3.06 Å
Structure data

37220

8kgg

EMDB-37220, PDB-8kgg:
LPS-bound P2Y10 in complex with G13
Method: EM (single particle) / Resolution: 3.06 Å

Chemicals

ChemComp-WJS:
(2~{S})-2-$l^{4}-azanyl-3-[[(2~{R})-3-octadecanoyloxy-2-oxidanyl-propoxy]-oxidanyl-oxidanylidene-$l^{6}-phosphanyl]oxy-propanoic acid

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / GPCR-G-protein complex

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