Domains of β₁ and β₂ adrenergic receptors to bind subtype selective agonists

We studied the binding region of several β₁ and β₂ selective agonists by using chimeric β₁ and β₂ARs, and point-mutated β₂ adrenergic receptors (ARs). By replacing a single transmembrane domain (TMD) of β₁AR (or β2AR) with the corresponding region of β₂AR (or β₁AR), we found that β₂ or β₁ selectivities were determined by TMD2 and TMD7 of β₂AR or by TMD2 of β₁AR, respectively. Alanine-substituted β2AR mutants showed that tyrosine at position 308 in TMD7 played an important role in binding of β₂ selective agonists with high affinity. These data also suggested that the substituent on the amine portion was important for subtype selective agonist binding.