Stroud James C, Lopez-Rodriguez Cristina, Rao Anjana, Chen Lin
Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado 80309-0215, USA.
Nat Struct Biol. 2002 Feb;9(2):90-4. doi: 10.1038/nsb749.
Tonicity-responsive enhancer binding protein (TonEBP), also known as NFAT5, is a unique member of the NFAT family of transcription factors that regulates gene expression induced by osmotic stress in mammalian cells. Unlike monomeric members of the NFAT family, TonEBP exists as a homodimer and binds asymmetric TonE DNA sites; furthermore, the affinity of TonEBP for DNA is much lower than that of other NFAT proteins. How TonEBP recognizes the TonE site and regulates the activation of hypertonicity response genes has not been clear. Here we show that TonEBP adopts a NF-kappaB-like structure upon binding to DNA, providing a direct structural link between the NFAT and NF-kappaB family of transcription factors. We also show that TonEBP completely encircles its DNA target and present biochemical evidence that the DNA encirclement may lead to increased kinetic stability of the TonEBP-DNA complex. Thus, the list of proteins that bind DNA by encirclement is now expanded to include sequence-specific transcription factors.
渗透压反应增强子结合蛋白（TonEBP），也称为NFAT5，是转录因子NFAT家族的一个独特成员，可调节哺乳动物细胞中由渗透压应激诱导的基因表达。与NFAT家族的单体成员不同，TonEBP以同源二聚体形式存在，并结合不对称的TonE DNA位点；此外，TonEBP对DNA的亲和力远低于其他NFAT蛋白。TonEBP如何识别TonE位点并调节高渗反应基因的激活尚不清楚。在这里，我们表明TonEBP在与DNA结合时采用类NF-κB结构，在转录因子的NFAT和NF-κB家族之间提供了直接的结构联系。我们还表明，TonEBP完全环绕其DNA靶标，并提供了生化证据表明DNA环绕可能导致TonEBP-DNA复合物的动力学稳定性增加。因此，通过环绕结合DNA的蛋白质列表现在已扩展到包括序列特异性转录因子。
