Lysophospholipid stereoisomers exert distinct GPR55-mediated functions via different Gα subunits.

ABSTRACT: Vertebrate glycerophospholipids typically exhibit a glycerol-3-phosphate (G3P)-configured backbone corresponding to the R-configured stereoisomer at the sn-2 chiral center. We previously found that the lysoglycerophospholipid lyso-phosphatidyl-β-d-glucoside (LysoPtdGlc) with G3P configuration, R-LysoPtdGlc, is an endogenous ligand of the G protein-coupled receptor GPR55, acting as an axon guidance cue via GPR55-Gα₁₃ signaling. However, LysoPtdGlc is hydrolytically derived from phosphatidyl-β-d-glucoside (PtdGlc), which exists in vivo in a 6:1 mixture of two stereoisomers, G3P-configured R-PtdGlc and glycerol-1-phosphate-configured S-PtdGlc. To test whether the stereoconfiguration of LysoPtdGlc influences its biological activity, we combined molecular dynamics simulations of GPR5

SUBMITTER: Guy AT 

PROVIDER: S-EPMC12268648 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature