5gli

Publication Abstract from PubMed

Endothelin, a 21-amino-acid peptide, participates in various physiological processes, such as regulation of vascular tone, humoral homeostasis, neural crest cell development and neurotransmission. Endothelin and its G-protein-coupled receptor are involved in the development of various diseases, such as pulmonary arterial hypertension, and thus are important therapeutic targets. Here we report 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 for the isopeptide selectivity between endothelin-1 and -3. Transmembrane helices 1, 2, 6 and 7 move and envelop the entire endothelin peptide, in a virtually irreversible manner. The agonist-induced conformational changes are propagated to the receptor core and the cytoplasmic G-protein coupling interface, and probably induce conformational flexibility in TM6. A comparison with the M2 muscarinic receptor suggests a shared mechanism for signal transduction in class A G-protein-coupled receptors.

Activation mechanism of endothelin ETB receptor by endothelin-1.,Shihoya W, Nishizawa T, Okuta A, Tani K, Dohmae N, Fujiyoshi Y, Nureki O, Doi T Nature. 2016 Sep 5;537(7620):363-368. doi: 10.1038/nature19319. PMID:27595334^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.