Identification of a Conformational Equilibrium That Determines the Efficacy and Functional Selectivity of the μ-Opioid Receptor
Dr. Junya Okude, Dr. Takumi Ueda, Dr. Yutaka Kofuku, Motohiko Sato, Naoyuki Nobuyama, Keita Kondo, Yutaro Shiraishi, Takuya Mizumura, Kento Onishi, Mei Natsume, Dr. Masahiro Maeda, Dr. Hideki Tsujishita, Dr. Takefumi Kuranaga, Prof. Dr. Masayuki Inoue and Prof. Dr. Ichio Shimada
Article first published online: 16 NOV 2015 | DOI: 10.1002/anie.201508794
An open and closed case: NMR analysis of different ligand-bound states of the μ-opioid receptor revealed that the intracellular cavity of the receptor exists in an equilibrium between closed and multiple open conformations, and that the population of each open conformation determines the G-protein- and β-arrestin-mediated signaling levels (see picture). These findings provide structural insight into the biased signaling of G-protein-coupled receptors.