GPCRs: Lipid-Dependent Membrane Receptors That Act as Drug Targets

Figure 1

A schematic representation of G protein-coupled receptor (GPCR) and its signaling. GPCRs are integral membrane proteins with seven transmembrane domains. A consequence of having odd number of transmembrane passes is that the amino and carboxy terminals are localized on opposite sides of the cellular membrane. The helices are often tilted resulting in compact structure due to helix-helix interaction and packing. GPCRs are activated by a wide variety of ligands that include biogenic amines, amino acids, ions, lipids, peptides, and various exogenous ligands such as odorants, pheromones, and even photons. Although the ligand shown here (in black) binds at the transmembrane region of the receptor, there are ligands that bind at the extracellular region of the receptor, depending on the receptor type. Upon binding to specific ligands, GPCRs activate heterotrimeric G proteins (consisting of , , and subunits). Activated G proteins regulate diverse signaling cascades, depending on their subtype (, , , and families). As a consequence, these receptors mediate multiple physiological processes such as neurotransmission, cellular metabolism, secretion, cellular differentiation, growth, inflammatory, and immune responses. See text for more details.