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, cholec ystokinin, to its G protein-coupled receptor is of substantial interest and may contribute to the successful production and refinement of receptor-act ive drugs. A number of methodological approaches provide complementary data to contribute to these insights. These include receptor mutagenesis, ligan d structure-activity data, conformational analysis of ligand and receptor f ragments, and photoaffinity labeling. In this work, we compare and contrast each of these methods and provide our current view of the cumulative impac t of the current data on molecular conformational models of the agonist-occ upied type A cholecystokinin receptor. These support the key roles played b y extracellular loop and tail regions of this receptor for binding its natu ral peptide ligand. (C) 2001 Elsevier Science Inc. All rights reserved.