Figure 6. Possible sequence of β₂AR-Gs complex formation.

a, b, Comparison of the β₂AR-Gs structure (green and gold) with metarhodopsin II³¹ (PDB ID: 3PQR) (purple) bound with the carboxyl-terminal peptide of transducin (blue). TM7 has been omitted in panel a to better visualize the G proteins. c, Cartoon of the β₂AR-Gαs peptide fusion construct used in the binding experiments (d). d, Competition binding experiments between [³H]-DHA and full agonist isoproterenol. Top panel shows binding data (reproduced from Rasmussen et al., 2011¹²) on β₂AR reconstituted in HDL particles with and without Gs heterotrimer. The fraction of β₂AR in the K_{i high} state for the β₂AR with Gs is 0.55. Bottom panel shows binding to β₂AR and a β₂AR-Gαs peptide fusion expressed in Sf9 cell membranes. The fraction of β₂AR in the K_{i high} state for the β₂AR-Gαs peptide fusion is 0.68. e, The initial interaction of agonist bound β₂AR and GαsRas may involve an orientation of the carboxyl-terminus of GαsRas similar to that of the carboxyl-terminal peptide of transducin in the structure of metarhodopsin II. f, The final position of GαsRas on the β₂AR as observed in the β₂AR-Gs complex.