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.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)