PtdIns(4,5)P₂ stabilizes active states of GPCRs and enhances selectivity of G-protein coupling.

ABSTRACT: G-protein-coupled receptors (GPCRs) are involved in many physiological processes and are therefore key drug targets¹. Although detailed structural information is available for GPCRs, the effects of lipids on the receptors, and on downstream coupling of GPCRs to G proteins are largely unknown. Here we use native mass spectrometry to identify endogenous lipids bound to three class A GPCRs. We observed preferential binding of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P₂) over related lipids and confirm that the intracellular surface of the receptors contain hotspots for PtdIns(4,5)P₂ binding. Endogenous lipids were also observed bound directly to the trimeric Gα_sβγ protein complex of the adenosine A_2A receptor (A_2AR) in

SUBMITTER: Yen HY 

PROVIDER: S-EPMC6059376 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature