Structural basis of antagonist selectivity in endothelin receptors.

ABSTRACT: Endothelins and their receptors, ET_A and ET_B, play vital roles in maintaining vascular homeostasis. Therapeutically targeting endothelin receptors, particularly through ET_A antagonists, has shown efficacy in treating pulmonary arterial hypertension (PAH) and other cardiovascular- and renal-related diseases. Here we present cryo-electron microscopy structures of ET_A in complex with two PAH drugs, macitentan and ambrisentan, along with zibotentan, a selective ET_A antagonist, respectively. Notably, a specialized anti-ET_A antibody facilitated the structural elucidation. These structures, together with the active-state structures of ET-1-bound ET_A and ET_B, and the agonist BQ3020-bound ET_B, in comp

SUBMITTER: Hou J 

PROVIDER: S-EPMC11286772 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature