Function of WW domains as phosphoserine- or phosphothreonine-binding modules
Function of WW domains as phosphoserine- or phosphothreonine-binding modules
复制标题
DOI：
10.1126/science.283.5406.1325
复制
发表时间：
1999-02-26
期刊：
影响因子：
56.9
通讯作者：
Lu, KP
中科院分区：
文献类型：
--
作者：
Lu, PJ;Zhou, XZ;Lu, KP
蛋白质相互作用模块有助于确定信号转导事件的特异性，而蛋白质磷酸化可以调节这些模块组装成特定的信号复合体。虽然已经很好地描述了磷酸酪氨酸结合模块的特征，但还没有描述过磷酸丝氨酸或磷酸苏氨酸结合模块。WW结构域是存在于各种参与细胞信号或调控的蛋白质中的小蛋白质模块，WW结构域是必需的有丝分裂脯氨酰异构酶Pin1和泛素连接酶Nedd4的WW结构域，以磷酸化依赖的方式与包括酶的生理底物在内的磷酸蛋白结合。Pin1的WW结构域作为一个磷酸丝氨酸或磷酸苏氨酸结合模块，具有与SRC同源2结构域相似的性质，在体外与其底物相互作用并在体内发挥其基本功能需要磷酸丝氨酸或磷酸苏氨酸结合活性。
Protein-interacting modules help determine the specificity of signal transduction events, and protein phosphorylation can modulate the assembly of such modules into specific signaling complexes. Although phosphotyrosine-binding modules have been well-characterized, phosphoserine- or phosphothreonine-binding modules have not been described. WW domains are small protein modules found in various proteins that participate in cell signaling or regulation, WW domains of the essential mitotic prolyl isomerase Pin1 and the ubiquitin ligase Nedd4 bound to phosphoproteins, including physiological substrates of enzymes, in a phosphorylation-dependent manner. The Pin1 WW domain functioned as a phosphoserine- or phosphothreonine-binding module, with properties similar to those of SRC homology 2 domains, Phosphoserine- or phosphothreonine-binding activity was required for Pin1 to interact with its substrates in vitro and to perform its essential function in vivo.