A G protein gamma subunit peptide stabilizes a novel muscarinic receptor state.
A prenylated peptide specific to the C terminal tail of a G protein gamma subunit type, gamma5, inhibits activation of a G protein by the M2 muscarinic receptor. The gamma5 peptide was tested for direct effects on the M2 receptor's properties. The wild type gamma5 peptide reduced the affinity of M2 for the agonist, carbachol, more than 5-fold in an antagonist displacement assay. The peptide was inactive when its amino acid sequence was scrambled or when it was unprenylated. Although the wild type peptide reduced the affinity of M2 for the antagonist QNB, it had no effect on the antagonists NMS or atropine. These results suggest that in the presence of the peptide the M2 receptor adopts a novel conformational state that affects the ligand binding surface. The results also suggest that the G protein gamma5 subunit tail interacts with a receptor.
Azpiazu
I
I
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Gautam
N
N
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000378:metabolism; D016466:CHO Cells; D002217:Carbachol / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000502:physiology*; D019832:N-Methylscopolamine / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D017368:Protein Prenylation; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D043585:Receptor, Muscarinic M2 / Q000819:agonists / Q000187:drug effects* / Q000502:physiology
D010446:Peptide Fragments; D043585:Receptor, Muscarinic M2; D011813:Quinuclidinyl Benzilate; D001285:Atropine; D002217:Carbachol; D051960:GTP-Binding Protein alpha Subunit, Gi2; D000109:Acetylcholine; D019832:N-Methylscopolamine