Peptide fragment of the m3 muscarinic acetylcholine receptor activates G(q) but not G(i2).
G(q), a heterotrimeric guanine nucleotide-binding protein, plays important roles such as the regulation of calcium mobilization and cell proliferation. This protein is considered as a promising drug target for the treatment of cardiac hypertrophy. Selective activation of G(q) would be quite useful for analyzing the role of G(q) in signaling pathways. We synthesized m3i3c-a peptide with 16 amino acid residues that corresponds to the junction between the C-terminus of the third intracellular loop and the sixth transmembrane helix (TM-VI) of human m3 muscarinic acetylcholine receptor, which couples to G(q) but not G(i2). At micromolar concentrations, this peptide was found to activate G(q) but not G(i2). This peptide is the first small compound that selectively activates G(q) but not G(i2).
Kubota
Makoto
M
Department of Chemistry and Chemical Biology, Graduate School of Engineering, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515, Japan.
Wakamatsu
Kaori
K
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001921:Brain; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000737:chemistry / Q000187:drug effects; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000737:chemistry / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017510:Protein Folding / Q000187:drug effects; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D043587:Receptor, Muscarinic M3 / Q000737:chemistry*; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; D043587:Receptor, Muscarinic M3; D051960:GTP-Binding Protein alpha Subunit, Gi2; D043802:GTP-Binding Protein alpha Subunits, Gq-G11