人EEN蛋白的结构预测和功能分析

采用基于神经网络的算法预测了我们自行克隆的新的白血病相关蛋白ＥＥＮ（ｅｘｔｒａ ｅｌｅｖｅｎｎｉｎｅｔｅｅｎ， ＥＥＮ）全长分子的二级结构，结果表明：ＥＥＮ 蛋白可能有三个结构域，Ｎ 端由三段α螺旋和短β折叠组成，中间为四段α螺旋组成的四螺旋结构，Ｃ端为ＳＨ３结构域，类似于在受体酪氨酸激酶信号传导途径中起重要作用的ＳＥＭ－５／ＧＲＢ２ Ｃ端ＳＨ３结构域；利用同源蛋白结构模拟的方法，模拟了ＥＥＮ ＳＨ３结构域的三维结构，结果表明：ＥＥＮ ＳＨ３结构域与ＳＥＭ－５／ＧＲＢ２ ＳＨ３结构域具有相近的结构，构成脯氨酸结合区的氨基酸非常保守．上述结果提示：ＥＥＮ 蛋白可能为新的信号蛋白，可能涉及新的信号传导途径或新的信号传导旁路，ＳＨ３结构域是其功能区域．

Structure Predication and Function Analysis of Human EEN Protein

The secondary structure of the deduced amino acid sequences of previously cloned human EEN gene has been predicated by neural network method. The results show that EEN protein may contain three domains: The NH2 terminal region contains three α helices and β sandwich, the central region contains four α helices, and the COOH terminal region contains an Src homology3(SH3) domain most similar to the C terminal SH3 domain found in the SEM 5/GRB2 family of genes involved in receptor tyrosine kinase signaling. The 3 dimensional structure of SH3 domain of EEN protein has been constructed by homology modeling method. The results show that the 3 dimensional structure of EEN SH3 domain is most similar to that of SEM 5/GRB 2 SH3 domain, and the amino acid sequences of SH3 domain which binds proline rich motifs in ligand protein are highly conserved between EEN protein and SEM 5/GRB2 proteins. These results suggest that EEN protein may be a new signal protein, involved in new signal transduction pathway or para pathway, and SH3 domain is its functional domain.