Crystal structure of the Bach1 BTB domain and its regulation of homodimerization
Crystal structure of the Bach1 BTB domain and its regulation of homodimerization
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DOI：
10.1111/j.1365-2443.2008.01259.x
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发表时间：
2009-02
期刊：
影响因子：
2.1
通讯作者：
N. Ito;Miki Watanabe-Matsui;K. Igarashi;K. Murayama
中科院分区：
文献类型：
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作者：
N. Ito;Miki Watanabe-Matsui;K. Igarashi;K. Murayama
BTB/POZ结构域被称为蛋白质-蛋白质相互作用基序，介导同源二聚体和高阶自缔合。含有BTB结构域的蛋白质存在于整个真核生物中;然而，关于决定BTB结构域的寡聚状态的机制的信息很少。为了解决这个问题，我们确定了小鼠Bach 1 BTB结构域的X射线结构。本结构类似于先前确定的BTB结构域折叠，包括人Bach 1 BTB结构域;然而，存在不同的结构特征，例如新型同二聚体相互作用表面。发现同二聚体的形成涉及一种新的氢键网络和扭结N末端（N钩）的疏水表面与配偶体的C末端残基之间的相互作用。N-hook的缺失导致同二聚体在溶液中转化为单体，表明N-hook促进了mBach 1 BTB结构域的同二聚化。我们还发现，Bach 2的BTB结构域（一种与Bach 1高度相关的蛋白质）由于在N钩处插入短肽而以单体形式存在。这些结果代表了BTB结构域同源二聚化的关键调节元件的第一个例子。
The BTB/POZ domain is known as a protein–protein interaction motif that mediates homodimer and higher order self‐associations. Proteins containing the BTB domain exist throughout eukaryotes; however, there is little information about the mechanism that determines the oligomeric state of the BTB domain. To address this question, we have determined the X‐ray structure of the mouse Bach1 BTB domain. The present structure is similar to the previously determined BTB domain folds, including the human Bach1 BTB domain; however, distinct structural features are present, such as a novel homodimer interaction surface. The homodimer formation was found to involve a novel hydrogen bond network and interactions between hydrophobic surfaces of the kinked N‐terminus (N‐hook) and the partner's C‐terminal residues. The deletion of the N‐hook resulted in the conversion of the homodimer into a monomer in solution, indicating that the N‐hook promotes the homodimerization of the mBach1 BTB domain. We have also found that the BTB domain of Bach2, a protein highly related to Bach1, is present as a monomer due to a short peptide insertion at the N‐hook. These results represent the first example of the key modulatory element of BTB domain homodimerization.