Insights into the binding and activation sites of the receptors for cholecystokinin and gastrin

Abstract : CCK receptors represent potential targets in a number of diseases. Knowledge of CCK receptor binding sites is a prerequisite for the understanding of the molecular basis for their ligand recognition, partial agonism, ligand-induced trafficking of signalling. In the current paper, we report studies from our laboratory and others which have provided new data on the molecular basis of the pharmacology and functioning of CCK1 and CCK2 receptors. It has been shown that: 1) homologous regions of the two receptors are involved in the binding site of CCK, however, positioning of CCK slightly differs in agreement with distinct pharmacophores of CCK toward the two receptors and receptor sequence variations; 2) Binding sites of most of non-peptide agonists/ antagonist are buried in the pocket formed by transmembrane helices and overlap that of CCK; Aromatic amino acids within and near the binding site, especially in helix VI, are involved in receptor activation; 4) Like for other members of family A of G-protein coupled receptors, residues of the binding sites as well as of conserved motifs such as E/DRY, NPXXY are crucial for receptor activation.
Type de document :
Article dans une revue
Regulatory Peptides, Elsevier, 2008, 145 (1-3), pp.17-23. 〈10.1016/j.regpep.2007.09.024〉
Liste complète des métadonnées

https://hal.inria.fr/inria-00188603
Contributeur : Malika Smail-Tabbone <>
Soumis le : dimanche 18 novembre 2007 - 22:36:24
Dernière modification le : jeudi 11 janvier 2018 - 06:19:54

Identifiants

Collections

Citation

Magali Foucaud, Elodie Archer-Lahlou, Esther Marco, Irina G. Tikhonova, Bernard Maigret, et al.. Insights into the binding and activation sites of the receptors for cholecystokinin and gastrin. Regulatory Peptides, Elsevier, 2008, 145 (1-3), pp.17-23. 〈10.1016/j.regpep.2007.09.024〉. 〈inria-00188603〉

Partager

Métriques

Consultations de la notice

269