Structure of the Ets-1 pointed domain and mitogen-activated protein kinase phosphorylation site
Structure of the Ets-1 pointed domain and mitogen-activated protein kinase phosphorylation site
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DOI：
10.1073/pnas.95.21.12129
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发表时间：
1998-10-13
影响因子：
11.1
通讯作者：
McIntosh, LP
中科院分区：
文献类型：
--
作者：
Slupsky, CM;Gentile, LN;McIntosh, LP
尖（PNT）域和一个相邻的促分裂原活化蛋白（MAP）激酶磷酸化位点被定义的ets转录因子的一个子集之间的序列保守性，并牵连在两个监管策略，蛋白质相互作用和翻译后修饰，分别。通过使用NMR，我们已经确定了110个残基的片段的小鼠Ets-1，其中包括PNT结构域和MAP激酶位点的结构。Ets-1 PNT结构域形成单体五螺旋束。该结构不同于任何已知的DNA或蛋白质结合模块，包括针对ets蛋白TEL的PNT结构域提出的螺旋-环-螺旋折叠。MAP激酶位点位于Ets-1片段的非磷酸化和磷酸化形式的高度灵活区域。磷酸化既不改变PNT结构域的结构也不改变其单体状态。这些结果表明Ets-1 PNT结构域在异型蛋白质相互作用中起作用，并支持靶点识别与MAP激酶位点的结构化偶联的可能性。
The Pointed (PNT) domain and an adjacent mitogen-activated protein (MAP) kinase phosphorylation site are defined by sequence conservation among a subset of ets transcription factors and are implicated in two regulatory strategies, protein interactions and posttranslational modifications, respectively. By using NMR, we have determined the structure of a 110-residue fragment of murine Ets-1 that includes the PNT domain and MAP kinase site. The Ets-1 PNT domain forms a monomeric five-helix bundle. The architecture is distinct from that of any known DNA- or protein-binding module, including the helix-loop-helix fold proposed for the PNT domain of the ets protein TEL. The MAP kinase site is in a highly flexible region of both the unphosphorylated and phosphorylated forms of the Ets-1 fragment. Phosphorylation alters neither the structure nor monomeric state of the PNT domain. These results suggest that the Ets-1 PNT domain functions in heterotypic protein interactions and support the possibility that target recognition is coupled to structuring of the MAP kinase site.