Figure 1.

Schematic representation of GPCR activation. Prior to ligand binding, the receptor is in an apo-state (receptor is in white). Upon the binding of an antagonist (red circle) to a receptor, there is no activation (receptor is in red). Upon the binding of an agonist (green circle), the receptor is in the pre-activation state (receptor is in yellow), and the G protein heterotrimer binds to the active receptor (active receptor is in green). The exchange of GDP for GTP in the G protein α subunit leads to dissociation and interaction with downstream effectors such as the Gα subunit with the adenylyl cyclase (AC) and Gβγ subunits that activate ion channels. Pre-activated receptors can also signal through arrestins. The phosphorylation of the receptor C-terminal tail (yellow circle) by G protein-coupled receptor kinase (GRK) binding (active receptor is in green) promotes arrestin recruitment (active receptor is in green), which can internalize the phosphorylated receptor. Gray dashed circles highlight the common binding pocket of the receptor where the α5-helix (blue cartoon) of the Gα subunit and the finger loop (purple cartoon) of arrestin bind upon the activation of the receptor (grey cartoon). The G proteins, GRK and arrestin are shown in blue, pink and purple, respectively. The apo, inactive, agonist-bound and active states of the receptor are shown in white, red, yellow, and green, respectively.