Mutational analysis of muscarinic acetylcholine receptors: structural basis of ligand/receptor/G protein interactions.
Molecular cloning studies have revealed the existence of five molecularly distinct muscarinic acetylcholine receptors (m1-m5), which differ in their tissue distribution, ligand binding properties, and functional profiles. Structurally (and functionally), the muscarinic receptors are members of the superfamily of G protein-coupled receptors. A variety of different mutagenesis techniques have been used to study the molecular basis of muscarinic receptor function. This approach has led to the identification of distinct receptor domains (or individual amino acids) predicted to play key roles in ligand binding, agonist-dependent receptor activation, and G protein coupling. Since all G protein-linked receptors share a similar molecular architecture, the information gained from the mutational analysis of muscarinic receptors should help delineate functionally important regions of other members of this receptor family.
Wess
J
J
Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
D000109:Acetylcholine / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011976:Receptors, Muscarinic / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship
D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins; D000109:Acetylcholine