Phosphorylation-induced conformation of β2-adrenoceptor related to arrestin recruitment revealed by NMR

Yutaro Shiraishi, Mei Natsume, Yutaka Kofuku, Shunsuke Imai, Kunio Nakata, Toshimi Mizukoshi, Takumi Ueda, Hideo Iwaï and Ichio Shimada ()
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Yutaro Shiraishi: The University of Tokyo
Mei Natsume: The University of Tokyo
Yutaka Kofuku: The University of Tokyo
Shunsuke Imai: The University of Tokyo
Kunio Nakata: Institute for Innovation, Ajinomoto Co., Inc
Toshimi Mizukoshi: Institute for Innovation, Ajinomoto Co., Inc
Takumi Ueda: The University of Tokyo
Hideo Iwaï: University of Helsinki
Ichio Shimada: The University of Tokyo

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: 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 β2-adrenoceptor (β2AR) and the phosphorylated β2AR–β-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 β-arrestin-bound state. The phosphorylation-induced structures revealed in this study propose a conserved structural motif of GPCRs that enables β-arrestin to recognize dozens of GPCRs.

Date: 2018
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DOI: 10.1038/s41467-017-02632-8

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