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Manifold active‐state conformations in GPCRs: Agonist‐activated constitutively active mutant AT 1 receptor preferentially couples to Gq compared to the wild‐type AT 1 receptor
Author(s) -
Lee ChangWoo,
Hwang Si Ae,
Jang Sei-Heon,
Chung Hye-Shin,
Bhat Manjunatha B.,
Karnik Sadashiva S.
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.04.069
Subject(s) - receptor , g protein coupled receptor , enzyme linked receptor , agonist , angiotensin ii receptor type 1 , chemistry , mutant , 5 ht5a receptor , angiotensin ii , protease activated receptor 2 , wild type , interleukin 21 receptor , microbiology and biotechnology , biochemistry , biology , gene
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 β‐arrestin. In contrast, the agonist‐bound AT1 N111G mutant receptor preferentially couples to Gq and is inadequate in β‐arrestin recruitment.