Theoretical study of the electrostatically driven step of receptor-G protein recognition.

Détails

ID Serval
serval:BIB_3243FFB377C5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Theoretical study of the electrostatically driven step of receptor-G protein recognition.
Périodique
Proteins
Auteur(s)
Fanelli F., Menziani C., Scheer A., Cotecchia S., De Benedetti P.G.
ISSN
0887-3585 (Print)
ISSN-L
0887-3585
Statut éditorial
Publié
Date de publication
1999
Volume
37
Numéro
2
Pages
145-156
Langue
anglais
Résumé
This study proposes a theoretical model describing the electrostatically driven step of the alpha 1 b-adrenergic receptor (AR)-G protein recognition. The comparative analysis of the structural-dynamics features of functionally different receptor forms, i.e., the wild type (ground state) and its constitutively active mutants D142A and A293E, was instrumental to gain insight on the receptor-G protein electrostatic and steric complementarity. Rigid body docking simulations between the different forms of the alpha 1 b-AR and the heterotrimeric G alpha q, G alpha s, G alpha i1, and G alpha t suggest that the cytosolic crevice shared by the active receptor and including the second and the third intracellular loops as well as the cytosolic extension of helices 5 and 6, represents the receptor surface with docking complementarity with the G protein. On the other hand, the G protein solvent-exposed portions that recognize the intracellular loops of the activated receptors are the N-terminal portion of alpha 3, alpha G, the alpha G/alpha 4 loop, alpha 4, the alpha 4/beta 6 loop, alpha 5, and the C-terminus. Docking simulations suggest that the two constitutively active mutants D142A and A293E recognize different G proteins with similar selectivity orders, i.e., G alpha q approximately equal to G alpha s > G alpha i > G alpha t. The theoretical models herein proposed might provide useful suggestions for new experiments aiming at exploring the receptor-G protein interface.
Mots-clé
Amino Acid Sequence, Animals, Cattle, GTP-Binding Proteins/chemistry, Mice, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Conformation, Receptors, Adrenergic, alpha-1/chemistry, Sequence Alignment, Static Electricity
Pubmed
Web of science
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 13:17
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