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

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Lee C,Hwang SA,Jang SH,Chung HS,Bhat MB,Karnik SS

doi

10.1016/j.febslet.2007.04.069

subject

Has Abstract

pub_date

2007-05-29 00:00:00

pages

2517-22

issue

13

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(07)00468-1

journal_volume

581

pub_type

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