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 M215^5.54 and M279^6.41, 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.

中文翻译：

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核磁共振显示，磷酸化诱导的β2-肾上腺素受体构象与抑制蛋白募集有关。

受激动剂结合刺激的G蛋白偶联受体（GPCR）的C端区域被GPCR激酶磷酸化，磷酸化的GPCR与抑制蛋白结合，导致细胞反应。为了理解的形成基础的机制GPCR磷酸化抑制蛋白复合物，我们进行的NMR分析的磷酸化的β ₂肾上腺素能受体（β ₂ AR）和磷酸化的β ₂ AR-β抑制蛋白1复合物，在纳米盘的脂质双层。在这里，我们显示磷酸化的C末端区域粘附到跨膜区域或脂质的细胞内侧，并且C末端区域的磷酸化变构改变M215 ^5.54和M279 ^6.41周围的构象。分别位于跨膜螺旋5和6上。另外，我们发现由磷酸化诱导的构象类似于对应于β-arrestin结合状态的构象。这项研究揭示的磷酸化诱导的结构提出了GPCR的保守结构基序，使β-arrestin能够识别数十种GPCR。