Cryo-EM structure of the endothelin-1-ET_B-G_i complex.

ABSTRACT: The endothelin ET_B receptor is a promiscuous G-protein coupled receptor that is activated by vasoactive peptide endothelins. ET_B signaling induces reactive astrocytes in the brain and vasorelaxation in vascular smooth muscle. Consequently, ET_B agonists are expected to be drugs for neuroprotection and improved anti-tumor drug delivery. Here, we report the cryo-electron microscopy structure of the endothelin-1-ET_B-G_i complex at 2.8 Å resolution, with complex assembly stabilized by a newly established method. Comparisons with the inactive ET_B receptor structures revealed how endothelin-1 activates the ET_B receptor. The NPxxY motif, essential for G-protein activation, is not conserved in ET_B, resulting in a

SUBMITTER: Sano FK 

PROVIDER: S-EPMC10129325 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature