Figure 1. G protein cycle for the β₂AR-Gs complex.

a, Extracellular agonist binding to the β₂AR leads to conformational rearrangements of the cytoplasmic ends of transmembrane segments that enable the G_s heterotrimer (α, β, and γ) to bind the receptor. GDP is released from the α subunit upon formation of β₂AR-Gs complex. The GTP binds to the nucleotide-free α subunit resulting in dissociation of the α and βγ subunits from the receptor. The subunits regulate their respective effector proteins adenylyl cyclase (AC) and Ca²⁺ channels. The G_s heterotrimer reassembles from α and βγ subunits following hydrolysis of GTP to GDP in the α subunit. b, The purified nucleotide-free β₂AR-Gs protein complex maintained in detergent micelles. The Gαs subunit consists of two domains, the Ras domain (αRas) and the α-helical domain (αAH). Both are involved in nucleotide binding. In the nucleotide-free state, the αAH domain has a variable position relative the αRas domain.