Keeping G proteins at bay:: A complex between G protein-coupled receptor kinase 2 and Gβγ
Keeping G proteins at bay:: A complex between G protein-coupled receptor kinase 2 and Gβγ
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DOI：
10.1126/science.1082348
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发表时间：
2003-05-23
期刊：
影响因子：
56.9
通讯作者：
Tesmer, JJG
中科院分区：
文献类型：
--
作者：
Lodowski, DT;Pitcher, JA;Tesmer, JJG
异三聚鸟嘌呤核苷酸结合蛋白 (G 蛋白) 偶联受体激酶 (GRK) 对七螺旋受体的磷酸化是一种通用的调节机制，可导致 G 蛋白信号传导脱敏并激活替代信号传导途径。我们确定了牛 GRK2 与 G 蛋白 beta(1)gamma(2) 亚基复合物的晶体结构。我们的结果显示了GRK2的三个结构域——RGS（G蛋白信号传导调节器）同源结构域、蛋白激酶和pleckstrin同源结构域——如何整合各自的活性，并将酶募集到细胞膜上，其方向不仅促进受体磷酸化，而且还允许同时抑制Galpha和Gbetagamma亚基的信号传导。
The phosphorylation of heptahelical receptors by heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor kinases (GRKs) is a universal regulatory mechanism that leads to desensitization of G protein signaling and to the activation of alternative signaling pathways. We determined the crystallographic structure of bovine GRK2 in complex with G protein beta(1)gamma(2) subunits. Our results show how the three domains of GRK2-the RGS (regulator of G protein signaling) homology, protein kinase, and pleckstrin homology domains-integrate their respective activities and recruit the enzyme to the cell membrane in an orientation that not only facilitates receptor phosphorylation, but also allows for the simultaneous inhibition of signaling by Galpha and Gbetagamma subunits.