Hydrophilic side chains in the third and seventh transmembrane helical domains of human A2A adenosine receptors are required for ligand recognition.

ABSTRACT: Hydrophilic residues of the G protein-coupled human A2A adenosine receptor that are potentially involved in the binding of the ribose moiety of adenosine were targeted for mutagenesis. Residues in a T88QSS91 sequence in the third transmembrane helical domain (TM3) were individually replaced with alanine and other amino acids. Two additional serine residues in TM7 that were previously shown to be involved in ligand binding were mutated to other uncharged, hydrophilic amino acids. The binding affinity of agonists at T88 mutant receptors was greatly diminished, although the receptors were well expressed and bound antagonists similar to the wild-type receptor. Thus, mutations that are specific for diminishing the affinity of ribose-containing ligands (i.e., adenosine agonists) have been identi

SUBMITTER: Jiang Q 

PROVIDER: S-EPMC3418326 | biostudies-literature | 1996 Sep

REPOSITORIES: biostudies-literature