Structure of endothelin ET_B receptor-G_i complex in a conformation stabilized by unique NPxxL motif.

ABSTRACT: Endothelin type B receptor (ET_BR) plays a crucial role in regulating blood pressure and humoral homeostasis, making it an important therapeutic target for related diseases. ET_BR activation by the endogenous peptide hormones endothelin (ET)-1-3 stimulates several signaling pathways, including G_s, G_i/o, G_q/11, G_12/13, and β-arrestin. Although the conserved NPxxY motif in transmembrane helix 7 (TM7) is important during GPCR activation, ET_BR possesses the lesser known NPxxL motif. In this study, we present the cryo-EM structure of the ET_BR-G_i complex, complemented by MD simulations and functional studies. These investigations reveal an unusual movement of TM7 to the intracellular side during ET

SUBMITTER: Tani K 

PROVIDER: S-EPMC11484851 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature