NMR studies of CCK-8/CCK1 complex support membrane-associated pathway for ligand-receptor interaction.
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.
Giragossian
Craig
C
Department of Chemistry, Brown University, Providence, RI 02912, USA.
Pellegrini
Maria
M
Mierke
Dale F
DF
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
D008024:Ligands; D008565:Membrane Proteins; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D012844:Sincalide