A threonine residue in the seventh transmembrane domain of the human A1 adenosine receptor mediates specific agonist binding.

摘要: The A1 adenosine receptor is a member of the seven-transmembrane G protein-coupled, superfamily. This binds purine nucleoside with high affinity and inhibits activity adenylate cyclase. We have used site-directed mutagenesis functional expression studies to examine role threonine residue, located at position 277 in transmembrane domain VII human receptor. Mutation Thr-277 either serine or alanine resulted receptors that had essentially no change binding for selective antagonist 8-cyclo-pentyl-1,3-dipropylxanthine. modest (4.4-8.6-fold) but significant increases observed Ki values three agonists, namely N-(1-methyl-2-phenethyl)adenosine (R-PIA S-PIA) 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-beta-L- ribofuranuronamide) (NECA). However, mutation changes R-PIA S-PIA did result highly 437-fold increase NECA. demonstrates hydroxyl moiety mediates agonist not and, more specifically, this residue forms probable molecular contact site 5' substitution found