Theoretical study on receptor-G protein recognition: new insights into the mechanisms of the alpha1b-adrenergic recptor activation

Détails

ID Serval
serval:BIB_0C33F5F19851
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Theoretical study on receptor-G protein recognition: new insights into the mechanisms of the alpha1b-adrenergic recptor activation
Périodique
International Journal of Quantum Chemistry
Auteur(s)
Fanelli F., Menziani C., Scheer A., Cotecchia S., De Benedetti P. G.
ISSN
0020-7608
Statut éditorial
Publié
Date de publication
1999
Volume
73
Numéro
2
Pages
71-83
Langue
anglais
Résumé
This work compares the structural/dynamics features of the wild-type alb-adrenergic receptor (AR) with those of the D142A active mutant and the agonist-bound state. The two active receptor forms were compared in their isolated states as well as in their ability to form homodimers and to recognize the G alpha q beta 1 gamma 2 heterotrimer. The analysis of the isolated structures revealed that, although the mutation- and agonist-induced active states of the alpha 1b-AR are different, they, however, share several structural peculiarities including (a) the release of some constraining interactions found in the wild-type receptor and (b) the opening of a cytosolic crevice formed by the second and third intracellular loops and the cytosolic extensions of helices 5 and 6. Accordingly, also their tendency to form homodimers shows commonalties and differences. In fact, in both the active receptor forms, helix 6 plays a crucial role in mediating homodimerization. However, the homodimeric models result from different interhelical assemblies. On the same line of evidence, in both of the active receptor forms, the cytosolic opened crevice recognizes similar domains on the G protein. However, the docking solutions are differently populated and the receptor-G protein preorientation models suggest that the final complexes should be characterized by different interaction patterns.
Mots-clé
G proteins, adrenergic receptors, homology modeling, molecular dynamics, docking, electrostatic potential
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Création de la notice
24/01/2008 12:05
Dernière modification de la notice
03/03/2018 13:37
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