Characterization of the type A cholecystokinin receptor hormone-binding domain: use of contrasting and complementary methodologies.
Insights into the molecular basis of binding of the peptide hormone, cholecystokinin, to its G protein-coupled receptor is of substantial interest and may contribute to the successful production and refinement of receptor-active drugs. A number of methodological approaches provide complementary data to contribute to these insights. These include receptor mutagenesis, ligand structure-activity data, conformational analysis of ligand and receptor fragments, and photoaffinity labeling. In this work, we compare and contrast each of these methods and provide our current view of the cumulative impact of the current data on molecular conformational models of the agonist-occupied type A cholecystokinin receptor. These support the key roles played by extracellular loop and tail regions of this receptor for binding its natural peptide ligand.
Ding
X Q
XQ
Center for Basic Research in Digestive Diseases, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Miller
L J
LJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D008024:Ligands; D008956:Models, Chemical; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010455:Peptides / Q000737:chemistry; D019920:Photoaffinity Labels / Q000494:pharmacology; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000737:chemistry*
D008024:Ligands; D010455:Peptides; D019920:Photoaffinity Labels; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin