Snapin interacts with G-protein coupled receptor PKR2
Snapin interacts with G-protein coupled receptor PKR2
复制标题
Snapin 与 G 蛋白偶联受体 PKR2 相互作用
DOI：
10.1016/j.bbrc.2015.12.023
复制
发表时间：
2016
影响因子：
3.1
通讯作者：
Jia-Da Li
中科院分区：
文献类型：
--
作者：
Jian Song;Jie Li;Hua-die Liu;Wei Liu;Yong Feng;Xiao-Tao Zhou;Jia-Da Li
原激动素受体2(PKR2)是一种G蛋白偶联受体，已在Kallmann综合征和/或以青春期延迟和不育为特征的特发性性腺激素减退症患者中被发现突变。在本研究中，我们以PKR2 C末端(氨基酸333-384)为诱饵进行酵母双杂交筛选，确定Snapin是PKR2的一个新的相互作用伙伴。在GST下拉和免疫共沉淀研究中证实了Snapin和PKR2的相互作用。我们进一步证明了这种相互作用需要管理单元中的两个α-螺旋结构域。PKR2的相互作用基序被定位到YFK(343-345)和HWR(351-353)，它们具有相似的序列，即两个芳香氨基酸和一个碱性氨基酸。Snapin-PKR2相互作用的中断不影响PKR2的信号转导，但增加了配体诱导的降解，提示Snapin在PKR2的运输中发挥了作用。
Mutations in Prokineticin receptor 2 (PKR2), a G-protein-coupled receptor, have been identified in patients with Kallmann syndrome and/or idiopathic hypogonadotropic hypogonadism, characterized by delayed puberty and infertility. In this study, we performed yeast two-hybrid screening by using PKR2 C-terminus (amino acids 333–384) as a bait, and identified Snapin as a novel interaction partner for PKR2. The interaction of Snapin and PKR2 was confirmed in GST pull-down and co-immunoprecipitation studies. We further demonstrated that two α-helix domains in Snapin are required for the interaction. And the interactive motifs of PKR2 were mapped to YFK (343–345) and HWR (351–353), which shared a similar sequence of two aromatic amino acids followed by a basic amino acid. Disruption of Snapin-PKR2 interaction did not affect PKR2 signaling, but increased the ligand-induced degradation, implying a role of Snapin in the trafficking of PKR2.