Long Jia-Fu, Feng Wei, Wang Rui, Chan Ling-Nga, Ip Fanny C F, Xia Jun, Ip Nancy Y, Zhang Mingjie
Department of Biochemistry, Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Nat Struct Mol Biol. 2005 Aug;12(8):722-8. doi: 10.1038/nsmb958. Epub 2005 Jul 10.
Members of the X11/Mint family of multidomain adaptor proteins are composed of a divergent N terminus, a conserved PTB domain and a pair of C-terminal PDZ domains. Many proteins can interact with the PDZ tandem of X11 proteins, although the mechanism of such interactions is unclear. Here we show that the highly conserved C-terminal tail of X11alpha folds back and inserts into the target-binding groove of the first PDZ domain. The binding of this tail occludes the binding of other target peptides. This autoinhibited conformation of X11 requires that the two PDZ domains and the entire C-terminal tail be covalently connected to form an integral structural unit. The autoinhibited conformation of the X11 PDZ tandem provides a mechanistic explanation for the unique target-binding properties of the protein and hints at potential regulatory mechanisms for the X11-target interactions.
多结构域衔接蛋白X11/Mint家族的成员由一个差异较大的N端、一个保守的PTB结构域和一对C端PDZ结构域组成。许多蛋白质能够与X11蛋白的PDZ串联结构相互作用，尽管这种相互作用的机制尚不清楚。在此，我们表明，X11α高度保守的C端尾巴向后折叠并插入到第一个PDZ结构域的靶标结合凹槽中。该尾巴的结合会阻碍其他靶标肽的结合。X11的这种自抑制构象要求两个PDZ结构域和整个C端尾巴共价连接以形成一个完整的结构单元。X11 PDZ串联结构的自抑制构象为该蛋白独特的靶标结合特性提供了一种机理解释，并暗示了X11与靶标相互作用的潜在调控机制。
