met-195 of the cholecystokinin-A receptor interacts with the sulfated tyrosine of cholecystokinin and is crucial for receptor transition to high affinity state
| Autor: | Luis Moroder, Véronique Gigoux, Chantal Escrieut, Jean-Alain Fehrentz, Danielle Gully, Nicole Vaysse, Daniel Fourmy, Laurent Gouilleux, Bernard Maigret, Sandrine Silvente-Poirot |
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| Přispěvatelé: | Fehrentz, Jean-Alain, Biologie et pathologie digestive, Institut Louis Bugnard-Institut National de la Santé et de la Recherche Médicale (INSERM), laboratoire de chimie théorique, Laboratoire de Physico-Chimie Théorique (LPCT), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Amino-acides Peptides et Protéines (LAPP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), sanofi recherche, SANOFI Recherche, Max-Planck-Institut für Biochemie (MPIB), Max-Planck-Gesellschaft |
| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Models
Molecular Stereochemistry Inositol Phosphates Ligands Transfection Binding Competitive digestive system Biochemistry 03 medical and health sciences Methionine 0302 clinical medicine Sulfation Animals Tyrosine Binding site Cholecystokinin A receptor Receptor Molecular Biology ComputingMilieux_MISCELLANEOUS 030304 developmental biology Cholecystokinin chemistry.chemical_classification 0303 health sciences Binding Sites Molecular Structure [CHIM.ORGA]Chemical Sciences/Organic chemistry digestive oral and skin physiology Cell Biology [CHIM.ORGA] Chemical Sciences/Organic chemistry Receptor Cholecystokinin A Amino acid chemistry COS Cells Mutagenesis Site-Directed Receptors Cholecystokinin Leucine hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | HAL Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 1998, 273 (23), pp.14380-14386 |
| ISSN: | 0021-9258 1083-351X |
| Popis: | Sulfation of the tyrosine at the seventh position from the C terminus of cholecystokinin (CCK) is crucial for CCK binding to the CCK-A receptor. Using three-dimensional modeling, we identified methionine 195 of the CCK-A receptor as a putative amino acid in interaction with the aromatic ring of the sulfated tyrosine of CCK. We analyzed the role played by the two partners of this interaction. The exchange of Met-195 for a leucine caused a minor decrease (2. 8-fold) on the affinity of the high affinity sites for sulfated CCK-9, a strong drop (73%) of their number, and a 30-fold decrease on the affinity of the low and very low affinity sites for sulfated CCK-9, with no change in their number. The mutation also caused a 54-fold decrease of the potency of the receptor to induce inositol phosphates production. The high affinity sites of the wild-type CCK-A receptor were highly selective (800-fold) toward sulfated versus nonsulfated CCK, whereas low and very low affinity sites were poorly selective (10- and 18-fold). In addition, the M195L mutant bound, and responded to, sulfated CCK analogues with decreased affinities and potencies, whereas it bound and responded to nonsulfated CCK identically to the wild-type receptor. Thus, Met-195 interacts with the aromatic ring of the sulfated tyrosine to correctly position the sulfated group of CCK in the binding site of the receptor. This interaction is essential for CCK-dependent transition of the CCK-A receptor to a high affinity state. Our data should represent an important step toward the identification of the residue(s) of the receptor in interaction with the sulfate moiety of CCK and the understanding of the molecular mechanisms that govern CCK-A receptor activation. |
| Databáze: | OpenAIRE |
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