Muscarinic acetylcholine receptors contain two highly conserved tyrosine residues that are located within or at the extracellular border of the second transmembrane domain and are unique to this subfamily of G protein-coupled receptors. These tyrosine residues are located at positions 82 and 85 of the sequence of the m1 subtype of muscarinic receptors. In this article, we studied the involvement of these two residues in ligand binding to and agonist-induced activation of this receptor subtype using site-directed mutagenesis. Our data suggest for the first time an important role of these two tyrosines in muscarinic receptor function. Evidence is also provided that although the aromatic moiety of these tyrosine residues plays a role in antagonist binding, both this moiety and the tyrosine phenolic hydroxyl group are involved in agonist binding and receptor activation. The results are discussed in terms of a possible relationship of these two tyrosine residues and other conserved tyrosine moieties located in different transmembrane segments. All of these residues might contribute in concert, albeit to different degrees, to the process of ligand binding and receptor activation. The present findings are expected to further our current understanding of the muscarinic receptor domains involved in these processes.
|Original language||English (US)|
|Number of pages||10|
|Journal||Receptors & signal transduction|
|State||Published - 1996|