Integrating the puzzle pieces: The current atomistic picture of phospholipid–G protein coupled receptor interactions

A compelling question of how phospholipids interact with their target receptors has been of interest since the first receptor-mediated effects were reported. The recent report of a crystal structure for the S1P1 receptor in complex with an antagonist phospholipid provides interesting perspective on the insights that had previously been gained through structure–activity studies of the phospholipids, as well as modeling and mutagenesis studies of the receptors. This review integrates these varied lines of investigation in the context of their various contributions to our current understanding of phospholipid–receptor interactions. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.

► Phospholipid interactions with LPA and S1P receptors reflected in phospholipid SAR ► Integrated view of phospholipid receptor structures from experiments and modeling ► Protein–protein interactions mediated by C-terminal motifs in the LPA receptors