title: Molecular basis of agonist binding to the type A cholecystokinin receptor.
abstract: The receptors for cholecystokinin (CCK) peptides are guanine nucleotide-binding protein-coupled receptors in the rhodopsin/beta-adrenergic receptor family. The molecular basis of natural ligand binding to the type A CCK receptor has been studied using ligand structure-activity series, receptor mutagenesis, and photoaffinity labeling studies. These have focused attention on the extracellular loop and tail domains, with the most direct insights coming from intrinsic photoaffinity labeling studies. A model of the binding of CCK to this receptor is consistent with all these studies. This model places the carboxyl terminus of CCK adjacent to the amino-terminal tail outside of transmembrane segment 1, the mid-region of the peptide adjacent to the third extracellular loop outside of transmembrane segment 7, and includes a charge-charge interaction between peptide residue tyrosine-sulfate 27 and the arginine residue in the second extracellular loop of the receptor in position 197.
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic and Foundation, Rochester, MN 55905, USA. miller@mayo.edu
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Miller
authors.forename: Terry P
authors.initials: TP
authors.lastname: Lybrand
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D016296:Mutagenesis; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D011949:Receptors, Cholecystokinin