Structure of cholecystokinin receptor binding sites and mechanism of activation/inactivation by agonists/antagonists.
Delineation of CCK receptor binding sites is a prerequisite for the understanding of the molecular basis for ligand recognition, partial agonism, ligand-induced traffiking of receptor signalling. In the current paper, we illustrate how, in the past 5 years, studies from our laboratory and others have provided new data on the molecular basis of the pharmacology and functioning of CCK1 and CCK2 receptors. Available data on CCK1 and CCK2R binding sites indicate that 1) homologous regions of the two receptors are involved in the binding site of CCK, however, positioning of CCK slightly differs; 2) binding sites of non-peptide agonists/antagonist are buried in the pocket formed by transmembrane helices and overlap that of CCK and 3) residues of the binding sites as well as of conserved motifs such as E/DRY, NPXXY are crucial for receptor activation.
Fourmy
Daniel
D
INSERM U 531, Louis Bugnard Institute, CHU Rangueil, Bat. L3, 31403 Toulouse Cedex 4, France. Daniel.Fourmy@toulouse.inserm.fr
Escrieut
Chantal
C
Archer
Elodie
E
Galès
Céline
C
Gigoux
Véronique
V
Maigret
Bernard
B
Moroder
Luis
L
Silvente-Poirot
Sandrine
S
Martinez
Jean
J
Fehrentz
Jean-Alain
JA
Pradayrol
Lucien
L
D000595:Amino Acid Sequence; D001665:Binding Sites; D002766:Cholecystokinin / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
D008024:Ligands; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin