Manifold active-state conformations in GPCRs: agonist-activated constitutively active mutant AT1 receptor preferentially couples to Gq compared to the wild-type AT1 receptor.

The angiotensin II type I (AT(1)) receptor mediates regulation of blood pressure and water-electrolyte balance by Ang II. Substitution of Gly for Asn(111) of the AT(1) receptor constitutively activates the receptor leading to Gq-coupled IP(3) production independent of Ang II binding. The Ang II-activated conformation of the AT1(N111G) receptor was ...
proposed to be similar to that of the wild-type AT(1) receptor, although, various aspects of the Ang II-induced conformation of this constitutively active mutant receptor have not been systematically studied. Here, we provide evidence that the conformation of the active state of the wild-type and the constitutively active AT(1) receptors are different. Upon Ang II binding an activated conformation of the wild-type AT(1) receptor activates G protein and recruits beta-arrestin. In contrast, the agonist-bound AT1(N111G) mutant receptor preferentially couples to Gq and is inadequate in beta-arrestin recruitment.
Mesh Terms:
Amino Acid Substitution, Animals, Arrestins, Asparagine, Binding Sites, Calcium, Calcium Signaling, Cloning, Molecular, Glycine, Kinetics, Mutagenesis, Site-Directed, Protein Conformation, Rats, Receptor, Angiotensin, Type 1, Receptors, G-Protein-Coupled, Recombinant Proteins
FEBS Lett.
Date: May. 29, 2007
Download Curated Data For This Publication
151262
Switch View:
  • Interactions 2