Mutagenesis and modelling of the alpha(1b)-adrenergic receptor highlight the role of the helix 3/helix 6 interface in receptor activation.

Détails

ID Serval
serval:BIB_108D66B64137
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Mutagenesis and modelling of the alpha(1b)-adrenergic receptor highlight the role of the helix 3/helix 6 interface in receptor activation.
Périodique
Molecular Pharmacology
Auteur(s)
Greasley P.J., Fanelli F., Rossier O., Abuin L., Cotecchia S.
ISSN
0026-895X (Print)
ISSN-L
0026-895X
Statut éditorial
Publié
Date de publication
2002
Volume
61
Numéro
5
Pages
1025-1032
Langue
anglais
Résumé
Computer simulations on a new model of the alpha1b-adrenergic receptor based on the crystal structure of rhodopsin have been combined with experimental mutagenesis to investigate the role of residues in the cytosolic half of helix 6 in receptor activation. Our results support the hypothesis that a salt bridge between the highly conserved arginine (R143(3.50)) of the E/DRY motif of helix 3 and a conserved glutamate (E289(6.30)) on helix 6 constrains the alpha1b-AR in the inactive state. In fact, mutations of E289(6.30) that weakened the R143(3.50)-E289(6.30) interaction constitutively activated the receptor. The functional effect of mutating other amino acids on helix 6 (F286(6.27), A292(6.33), L296(6.37), V299(6.40,) V300(6.41), and F303(6.44)) correlates with the extent of their interaction with helix 3 and in particular with R143(3.50) of the E/DRY sequence.
Mots-clé
Amino Acid Substitution, Animals, COS Cells, Cercopithecus aethiops, Cricetinae, Models, Molecular, Mutagenesis, Protein Structure, Secondary, Receptors, Adrenergic, alpha-1/chemistry, Receptors, Adrenergic, alpha-1/genetics, Transfection
Pubmed
Web of science
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 12:37
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