Cholesterol, phospholipids, and lipid modifications play important roles in structural stability, ligand recognition, aggregation status, and signal transductions of GPCR and its downstream effector proteins. In recent years, although great progresses have been made in the study of GPCR structures and ligand-mediated activation mechanism, the understanding of membrane environment and membrane lipids on the regulation of GPCR function is still scarce.
In our recent papers, (1) the Go protein C351 site was modified by palmitoylation and mediated adhesion receptor GPR97 coupling with G protein; (2) phosphatidylinositol-4-phosphate (PI4P) is the molecular basis for the high constitutive activity of the 5-HT1A receptor. Our studies have shown that the 5-HT1A receptor has high constitutive activity and can form complexes with Gi proteins without the addition of an agonist. This discovery reveals the molecular mechanism of the high constituent activity of 5-HT1A receptor, which is of great significance for the functional study of 5-HT1A receptor; (3) phospholipid was first discovered as a structural molecule to enhance the stability of GABAB receptor. Phospholipids, as structural molecules, can enhance the stability of GABAB receptor. It was first found in the analysis of the structure of GABAB receptor under electron microscope that phospholipids are occupied in the TM domain of inactive and active GABAB, and recently determined GABAB-Gi complex, which is likely to be an essential structural molecule of GABAB receptor.