Structural basis for selectivity and diversity in angiotensin II receptors.

ABSTRACT: The angiotensin II receptors AT₁R and AT₂R serve as key components of the renin-angiotensin-aldosterone system. AT₁R has a central role in the regulation of blood pressure, but the function of AT₂R is unclear and it has a variety of reported effects. To identify the mechanisms that underlie the differences in function and ligand selectivity between these receptors, here we report crystal structures of human AT₂R bound to an AT₂R-selective ligand and to an AT₁R/AT₂R dual ligand, capturing the receptor in an active-like conformation. Unexpectedly, helix VIII was found in a non-canonical position, stabilizing the active-like state, but at the same time preventing the recruitment of G proteins or β-arrestin

SUBMITTER: Zhang H 

PROVIDER: S-EPMC5525545 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature