Molecular basis of agonist binding to the type A cholecystokinin receptor

Laurence J. Miller, Terry P. Lybrand

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The receptors for cholecystokinin (CCK) peptides are guanine nucleotide-binding protein-coupled receptors in the rhodopsin/β-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.

Original languageEnglish (US)
Pages (from-to)282-285
Number of pages4
JournalPharmacology and Toxicology
Volume91
Issue number6
DOIs
StatePublished - Dec 1 2002

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ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

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