Structural Mechanism of the Arrestin-3/JNK3 Interaction
Structural Mechanism of the Arrestin-3/JNK3 Interaction
复制标题
Arrestin-3/JNK3 相互作用的结构机制
DOI：
10.1016/j.str.2019.04.002
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发表时间：
2019
期刊：
影响因子：
5.7
通讯作者：
Chung Ka Young
中科院分区：
文献类型：
--
作者：
Park Ji Young;Qu Chang-xiu;Li Rui-rui;Yang Fan;Yu Xiao;Tian Zhao-mei;Shen Yue-mao;Cai Bo-yang;Yun Youngjoo;Sun Jin-peng;Chung Ka Young
抑制蛋白，除了脱敏GPCR诱导的G蛋白激活，还介导G蛋白的非依赖性信号通过与各种信号蛋白相互作用。其中，抑制蛋白通过支架化丝裂原活化蛋白激酶（MAPK）信号传导组分如MAPKKK、MAPKK和MAPK来调节MAPK信号传导。在这项研究中，我们研究了结合模式和arrestin-3和JNK 3之间的接口使用氢/氘交换质谱，19 F-NMR，和阿托655荧光猝灭技术。结果表明，arrestin-3的β1链是与JNK 3的主要和潜在的唯一相互作用位点。结果还表明，JNK 3激活环附近的C端半段区域形成了潜在的结合界面，该界面根据ATP结合状态而变化。由于抑制蛋白-3的β1链在其基础状态下被C末端链掩埋，因此C末端截短（即，抑制蛋白-3的预活化）促进抑制蛋白-3/JNK3相互作用。
Arrestins, in addition to desensitizing GPCR-induced G protein activation, also mediate G protein-independent signaling by interacting with various signaling proteins. Among these, arrestins regulate MAPK signal transduction by scaffolding mitogen-activated protein kinase (MAPK) signaling components such as MAPKKK, MAPKK, and MAPK. In this study, we investigated the binding mode and interfaces between arrestin-3 and JNK3 using hydrogen/deuterium exchange mass spectrometry,19F-NMR, and tryptophan-induced Atto 655 fluorescence-quenching techniques. Results suggested that the β1 strand of arrestin-3 is the major and potentially only interaction site with JNK3. The results also suggested that C-lobe regions near the activation loop of JNK3 form the potential binding interface, which is variable depending on the ATP binding status. Because the β1 strand of arrestin-3 is buried by the C-terminal strand in its basal state, C-terminal truncation (i.e., pre-activation) of arrestin-3 facilitates the arrestin-3/JNK3 interaction.