Active state structures of G protein-coupled receptors highlight the similarities and differences in the G protein and arrestin coupling interfaces
Active state structures of G protein-coupled receptors highlight the similarities and differences in the G protein and arrestin coupling interfaces
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DOI：
10.1016/j.sbi.2017.04.010
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发表时间：
2017-08-01
影响因子：
6.8
通讯作者：
Tate, Christopher G.
中科院分区：
文献类型：
--
作者：
Carpenter, Byron;Tate, Christopher G.
G蛋白偶联受体(GPCRs)通过异源三聚体G蛋白和阻滞素对一系列细胞外刺激做出反应来调节细胞信号的传递。在与细胞内信号蛋白结合的活性构象中确定GPCRs的结构已被证明是非常具有挑战性的。尽管如此，去年已经发表了三种新的GPCRs结构，即与工程G蛋白结合的腺苷A(2A)受体(A(2A)R)，与视觉arrestin结合的视蛋白，以及与G蛋白类似的纳米体结合的u，阿片受体(Mu OR)。这些结构为导致GPCRs激活的事件序列提供了新的见解，并突出了GPCRs和不同信号蛋白之间界面结构的相似和差异。
G protein-coupled receptors (GPCRs) regulate cellular signalling through heterotrimeric G proteins and arrestins in response to an array of extracellular stimuli. Structure determination of GPCRs in an active conformation bound to intracellular signalling proteins has proved to be highly challenging. Nonetheless, three new structures of GPCRs in an active state have been published during the last year, namely the adenosine A(2A) receptor (A(2A)R) bound to an engineered G protein, opsin bound to visual arrestin and the mu, opioid receptor (mu OR) bound to a G protein-mimicking nanobody. These structures have provided novel insight into the sequence of events leading to GPCR activation, and have highlighted both similarities and differences in the structure of the interface between GPCRs and different signalling proteins.