The activation process of the alpha1B-adrenergic receptor: potential role of protonation and hydrophobicity of a highly conserved aspartate.

Détails

ID Serval
serval:BIB_921172AEBC6F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The activation process of the alpha1B-adrenergic receptor: potential role of protonation and hydrophobicity of a highly conserved aspartate.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Scheer A., Fanelli F., Costa T., De Benedetti P.G., Cotecchia S.
ISSN
0027-8424 (Print)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
1997
Volume
94
Numéro
3
Pages
808-813
Langue
anglais
Résumé
In this study, a quantitative approach was used to investigate the role of D142, which belongs to the highly conserved E/DRY sequence, in the activation process of the alpha1B-adrenergic receptor (alpha1B-AR). Experimental and computer-simulated mutagenesis were performed by substituting all possible natural amino acids at the D142 site. The resulting congeneric set of proteins together with the finding that all the receptor mutants show various levels of constitutive (agonist-independent) activity enabled us to quantitatively analyze the relationships between structural/dynamic features and the extent of constitutive activity. Our results suggest that the hydrophobic/hydrophilic character of D142, which could be regulated by protonation/deprotonation of this residue, is an important modulator of the transition between the inactive (R) and active (R*) state of the alpha1B-AR. Our study represents an example of quantitative structure-activity relationship analysis of the activation process of a G protein-coupled receptor.
Mots-clé
Adrenergic alpha-Agonists/metabolism, Adrenergic alpha-Antagonists/metabolism, Amino Acids/chemistry, Animals, Aspartic Acid/physiology, Binding, Competitive, COS Cells, Computer Simulation, Epinephrine/metabolism, Inositol Phosphates/biosynthesis, Ligands, Mutagenesis, Site-Directed, Prazosin/metabolism, Protein Structure, Tertiary, Protons, Receptors, Adrenergic, alpha-1/chemistry, Receptors, Adrenergic, alpha-1/genetics, Solvents, Structure-Activity Relationship
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 12:06
Dernière modification de la notice
08/05/2019 22:04
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