Experimental studies of wild type A(2A) receptor and cholesterol-binding receptor variants support a model for cholesterol as an allosteric modulator of G protein coupling

G protein-coupled receptors (GPCRs) comprise the largest known family of human receptors and are the targets of approximately a third of presently approved pharmaceuticals. Cholesterol is present in the cell membrane of eukaryotic cells, and variations in cholesterol concentrations within a single cell type have been implicated in disease pathologies such as Alzheimer's disease. A2AR contains have specific cholesterol binding motifs, such as the cholesterol consensus motif (CCM), which are predicted sites where membrane cholesterol interacts with the receptor.