G protein-coupled receptors (GPCRs) are the largest and most diverse group of membrane receptors in the body. They play a key role in a broad range of biological processes by binding to a wide variety of signaling molecules, yet they share a common architecture. GPCRs are comprised of seven transmembrane (TM) helices that span the cell membrane and intervening loops that are presented towards either the extracellular (EC) or intracellular (IC) environments. Agonists bind to GPCRs at an EC-facing binding pocket and initiate conformational changes that are propagated to the IC loops. This subsequently triggers downstream signaling via G-proteins or G-protein-independent pathways.
GPCR ligands often preferentially activate particular downstream pathways (signaling bias) and thus illicit different biological effects. This functional plasticity can be attributed to the intrinsic structural flexibility of GPCRs and the ability of signaling molecules to recognize and stabilize specific conformations.