<jats:title>Abstract</jats:title><jats:p>G protein-coupled receptors (GPCRs) bind to different G protein α-subtypes with varying degrees of selectivity. The mechanism by which GPCRs achieve this selectivity is still unclear. Using <jats:sup>13</jats:sup>C methyl methionine and <jats:sup>19</jats:sup>F NMR, we investigate the agonist-bound active state of β<jats:sub>1</jats:sub>AR and its ternary complexes with different G proteins in solution. We find the receptor in the ternary complexes adopts very similar conformations. In contrast, the full agonist-bound receptor active state assumes a conformation differing from previously characterised activation intermediates or from β<jats:sub>1</jats:sub>AR in ternary complexes. Assessing the kinetics of binding for the agonist-bound receptor with different G proteins, we find the increased affinity of β<jats:sub>1</jats:sub>AR for G<jats:sub>s</jats:sub> results from its much faster association with the receptor. Consequently, we suggest a kinetic-driven selectivity gate between canonical and secondary coupling which arises from differential favourability of G protein binding to the agonist-bound receptor active state.</jats:p>
