S100A16, a novel calcium-binding protein of the EF-hand superfamily
S100A16, a novel calcium-binding protein of the EF-hand superfamily
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DOI：
10.1074/jbc.m605798200
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发表时间：
2006-12-15
影响因子：
4.8
通讯作者：
Heizmann, Claus W.
中科院分区：
文献类型：
--
作者：
Sturchler, Emmanuel;Cox, Jos A.;Heizmann, Claus W.
S100 A16蛋白是EF-手型Ca ~（2+）结合蛋白中的一个新成员。S100蛋白具有细胞和组织特异性，通过与特异性靶蛋白相互作用参与多种细胞内和细胞外过程。在中枢神经系统中，S100蛋白与细胞增殖、分化、迁移和凋亡以及认知有关。S100蛋白成为主要的兴趣，因为它们与大脑病理学密切相关，例如抑郁症或阿尔茨海默病。在这里，我们报告的第一次纯化和生化特性的人和小鼠重组S100 A16蛋白。流动透析显示，这两个同源二聚体S100 A16蛋白结合两个Ca 2+离子与C-末端EF-手的每个亚基，人类蛋白质表现出2倍更高的亲和力。Trp荧光变化表明Ca 2+结合后直系同源蛋白质的构象变化，而与靶蛋白识别有关的疏水性斑块的形成仅发生在人S100 A16蛋白中。原位杂交分析和免疫组织化学显示，广泛分布在小鼠脑。此外，发现S100 A16表达是星形胶质细胞特异性的。最后，我们研究了S100 A16在人胶质母细胞瘤细胞中的细胞内定位。该蛋白质被发现积累在核仁内，并易位到细胞质中响应Ca 2+刺激。
S100A16 protein is a new and unique member of the EF-hand Ca2+-binding proteins. S100 proteins are cell- and tissue-specific and are involved in many intra- and extracellular processes through interacting with specific target proteins. In the central nervous system S100 proteins are implicated in cell proliferation, differentiation, migration, and apoptosis as well as in cognition. S100 proteins became of major interest because of their close association with brain pathologies, for example depression or Alzheimer's disease. Here we report for the first time the purification and biochemical characterization of human and mouse recombinant S100A16 proteins. Flow dialysis revealed that both homodimeric S100A16 proteins bind two Ca2+ ions with the C-terminal EF-hand of each subunit, the human protein exhibiting a 2-fold higher affinity. Trp fluorescence variations indicate conformational changes in the orthologous proteins upon Ca2+ binding, whereas formation of a hydrophobic patch, implicated in target protein recognition, only occurs in the human S100A16 protein. In situ hybridization analysis and immunohistochemistry revealed a widespread distribution in the mouse brain. Furthermore, S100A16 expression was found to be astrocyte-specific. Finally, we investigated S100A16 intracellular localization in human glioblastoma cells. The protein was found to accumulate within nucleoli and to translocate to the cytoplasm in response to Ca2+ stimulation.