title: NMR studies of CCK-8/CCK1 complex support membrane-associated pathway for ligand-receptor interaction.
abstract: The interaction of peptide ligands with their associated G-protein-coupled receptors has been examined by a number of different experimental approaches over the years. We have been developing an approach utilizing high-resolution NMR to determine the structural features of the peptide ligand, well-designed fragments of the receptor, and the ligand-receptor complexes formed upon titration of the peptide hormone. The results from these investigations provide evidence for a membrane-associated pathway for the initial interaction of peptide ligands with the receptor. Here, our results from the investigation of the interaction of CCK-8 with the CCK1 receptor are described. Our spectroscopic results clearly show that both CCK-8 and the regions of CCK1 with which it interacts are closely associated with the zwitterionic interface of the lipids utilized in our solution spectroscopic studies.
authors.affiliation: Department of Chemistry, Brown University, Providence, RI 02912, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Giragossian
authors.forename: Maria
authors.initials: M
authors.lastname: Pellegrini
authors.forename: Dale F
authors.initials: DF
authors.lastname: Mierke
mesh_terms: D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012844:Sincalide / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D008565:Membrane Proteins; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D012844:Sincalide