Phosphorylation-induced conformation of ?2-adrenoceptor related to arrestin recruitment revealed by NMR.
Related Articles Phosphorylation-induced conformation of ?2-adrenoceptor related to arrestin recruitment revealed by NMR.
Nat Commun. 2018 Jan 15;9(1):194
Authors: Shiraishi Y, Natsume M, Kofuku Y, Imai S, Nakata K, Mizukoshi T, Ueda T, Iwaï H, Shimada I
Abstract
The C-terminal region of G-protein-coupled receptors (GPCRs), stimulated by agonist binding, is phosphorylated by GPCR kinases, and the phosphorylated GPCRs bind to arrestin, leading to the cellular responses. To understand the mechanism underlying the formation of the phosphorylated GPCR-arrestin complex, we performed NMR analyses of the phosphorylated ?2-adrenoceptor (?2AR) and the phosphorylated ?2AR-?-arrestin 1 complex, in the lipid bilayers of nanodisc. Here we show that the phosphorylated C-terminal region adheres to either the intracellular side of the transmembrane region or lipids, and that the phosphorylation of the C-terminal region allosterically alters the conformation around M2155.54 and M2796.41, located on transemembrane helices 5 and 6, respectively. In addition, we found that the conformation induced by the phosphorylation is similar to that corresponding to the ?-arrestin-bound state. The phosphorylation-induced structures revealed in this study propose a conserved structural motif of GPCRs that enables ?-arrestin to recognize dozens of GPCRs.
PMID: 29335412 [PubMed - in process]
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