Structural insights into angiotensin receptor signaling modulation by balanced and biased agonists.

ABSTRACT: The peptide hormone angiotensin II regulates blood pressure mainly through the type 1 angiotensin II receptor AT₁ R and its downstream signaling proteins G_q and β-arrestin. AT₁ R blockers, clinically used as antihypertensive drugs, inhibit both signaling pathways, whereas AT₁ R β-arrestin-biased agonists have shown great potential for the treatment of acute heart failure. Here, we present a cryo-electron microscopy (cryo-EM) structure of the human AT₁ R in complex with a balanced agonist, Sar¹ -AngII, and G_q protein at 2.9 Å resolution. This structure, together with extensive functional assays and computational modeling, reveals the molecular mechanisms for AT₁ R signaling modulation and suggests that a

SUBMITTER: Zhang D 

PROVIDER: S-EPMC10233375 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature