标题：Structural Mechanism of the Arrestin-3/JNK3 Interaction
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, Ji 更多 作者机构：[Park, Ji Young; Yun, Youngjoo; Chung, Ka Young] Sungkyunkwan Univ, Sch Pharm, 2066 Seobu Ro, Suwon 16419, South Korea.; [Qu, Chang-xiu; Cai, Bo-yan 更多
通讯作者：Chung, KY;Sun, JP;Sun, JP;Sun, JP
通讯作者地址：[Chung, KY]Sungkyunkwan Univ, Sch Pharm, 2066 Seobu Ro, Suwon 16419, South Korea;[Sun, JP]Peking Univ, Key Lab Mol Cardiovasc Sci, Minist Educ, Dept P 更多
摘要：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, F-19-NMR, and tryptophan-induced Atto 655 fluorescence-quenching techniques. Results suggested that the beta 1 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 beta 1 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.