Angiotensin II receptor type 1 (AT1R) N111G mutant (AT1R-N111G)

The Angiotensin II receptor type 1 (AT1R) N111G mutant is a well-characterized constitutively active variant of the human AT1 receptor, which belongs to the G protein-coupled receptor (GPCR) superfamily (UniProt P30556). This specific mutation involves the substitution of asparagine at position 111 with glycine in the third transmembrane helix, a modification that disrupts the interhelical hydrogen bond network that normally stabilizes the receptor's inactive state (Noda et al., 1995). Consequently, the N111G mutant exhibits high levels of basal signaling activity through the Gq/11 pathway and recruits beta-arrestins even in the absence of its natural ligand, Angiotensin II (Boucard et al., 2003). In pharmacological research, this mutant serves as a critical tool for identifying inverse agonists, as many clinically used Angiotensin II receptor blockers (ARBs), such as olmesartan and candesartan, are able to suppress this constitutive activity (Miura et al., 2006). While the wild-type AT1 receptor is the primary therapeutic target for managing hypertension and heart failure, the N111G mutant provides a sensitized model for understanding receptor activation and the development of biased ligands.

Other names

AGTR1 N111GAT1 receptor N111GN111G-AT1RConstitutively active Angiotensin II type 1 receptor

Inverse agonism and competitive antagonism of the Angiotensin II type 1 receptor, suppressing both basal (constitutive) and ligand-induced signaling pathways.