Abstract:
:The angiotensin II type 1 (AT(1)) receptor is a G protein-coupled receptor that has a crucial role in the development of load-induced cardiac hypertrophy. Here, we show that cell stretch leads to activation of the AT(1) receptor, which undergoes an anticlockwise rotation and a shift of transmembrane (TM) 7 into the ligand-binding pocket. As an inverse agonist, candesartan suppressed the stretch-induced helical movement of TM7 through the bindings of the carboxyl group of candesartan to the specific residues of the receptor. A molecular model proposes that the tight binding of candesartan to the AT(1) receptor stabilizes the receptor in the inactive conformation, preventing its shift to the active conformation. Our results show that the AT(1) receptor undergoes a conformational switch that couples mechanical stress-induced activation and inverse agonist-induced inactivation.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Yasuda N,Miura S,Akazawa H,Tanaka T,Qin Y,Kiya Y,Imaizumi S,Fujino M,Ito K,Zou Y,Fukuhara S,Kunimoto S,Fukuzaki K,Sato T,Ge J,Mochizuki N,Nakaya H,Saku K,Komuro Idoi
10.1038/sj.embor.7401157subject
Has Abstractpub_date
2008-02-01 00:00:00pages
179-86issue
2eissn
1469-221Xissn
1469-3178pii
7401157journal_volume
9pub_type
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