Activation mechanism of endothelin ETB receptor by endothelin-1

The vasoconstricitor peptide endothelin and its G-protein-coupled receptor (GPCR) are involved in the development of various diseases, such as pulmonary arterial hypertension, so are important therapeutic targets. In this manuscript, the authors report the X-ray crystal structures of human endothelin type B receptor in the ligand-free form and in complex with the endogenous agonist endothelin-1. The structures and mutation analysis reveal the mechanism of the isopeptide selectivity between endothelin-1 and endothelin-3. Comparison with the M2 muscarinic receptor suggests a shared mechanism for signal transduction in class A GPCRs.