Molecular and genetic basis of beta2-adrenergic receptor function.
The beta(2 )-adrenergic receptor has been cloned, mutated, and recombinantly expressed such that many structural features involved in receptor function have been defined. Agonists bind in a pocket formed by transmembrane spanning domains 3, 5, and 6, where key contact points initiate receptor activation. An interaction with the beta-hydroxyl group of beta-agonists and Asn293 of the latter transmembrane domain is the basis of the stereoselectivity of R- vs S-isomers of catecholamine-like agonists. Sites within the receptor that serve to dampen the signal with continuous agonist exposure have also been identified and include sites for phosphorylation by protein kinase A and G-protein-coupled receptor kinases and structural features that direct the receptor toward degradation (downregulation). Several regions of the beta(2 )-adrenergic receptor show genetic diversity within the human population, such that expression, coupling, and agonist regulation may be different in individuals with these polymorphisms.
Liggett
S B
SB
Departments of Medicine (Pulmonary) and Pharmacology, University of Cincinnati College of Medicine, Ohio, USA.
D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2