Crystal structure of a junction between B-DNA and Z-DNA reveals two extruded bases
Crystal structure of a junction between B-DNA and Z-DNA reveals two extruded bases
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DOI：
10.1038/nature04088
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发表时间：
2005-10-20
期刊：
影响因子：
64.8
通讯作者：
Kim, KK
中科院分区：
文献类型：
--
作者：
Ha, SC;Lowenhaupt, K;Kim, KK
左手 Z-DNA 是双螺旋的较高能量形式，通过转录或展开核小体产生的负超螺旋来稳定 (1)。转录起始位点附近的区域通常包含有利于形成 Z-DNA (2) 的序列基序，启动子区域附近 Z-DNA 的形成会刺激转录 (3,4)。 Z-DNA 还可以通过特定的蛋白质结合来稳定；已鉴定出几种具有低纳摩尔结合常数的蛋白质 (5-9)。 Z-DNA 处于动态状态，由生理过程形成，然后松弛为右手 B-DNA(1)。每次 DNA 片段转变为 Z-DNA 时，都会形成两个 B-Z 连接。这些已被广泛研究(10-12)，但它们的结构未知。在这里，我们描述了通过 X 射线晶体学以 2.6 埃分辨率揭示的 B-Z 结的结构。 DNA 的 15 个碱基对片段的一端通过 Z-DNA 结合蛋白稳定在 Z 构象，而另一端仍然是 B-DNA。我们发现 B-DNA 和 Z-DNA 片段之间的碱基连续堆积，连接处有一个碱基对断裂，两侧的碱基被挤压（图 1）。这些挤出的碱基可能是DNA修饰的位点。
Left-handed Z-DNA is a higher-energy form of the double helix, stabilized by negative supercoiling generated by transcription or unwrapping nucleosomes(1). Regions near the transcription start site frequently contain sequence motifs favourable for forming Z-DNA(2), and formation of Z-DNA near the promoter region stimulates transcription(3,4). Z-DNA is also stabilized by specific protein binding; several proteins have been identified with low nanomolar binding constants(5-9). Z-DNA occurs in a dynamic state, forming as a result of physiological processes then relaxing to the right-handed B-DNA(1). Each time a DNA segment turns into Z-DNA, two B-Z junctions form. These have been examined extensively(10-12), but their structure was unknown. Here we describe the structure of a B-Z junction as revealed by X-ray crystallography at 2.6 angstrom resolution. A 15-base-pair segment of DNA is stabilized at one end in the Z conformation by Z-DNA binding proteins, while the other end remains B-DNA. Continuous stacking of bases between B-DNA and Z-DNA segments is found, with the breaking of one base pair at the junction and extrusion of the bases on each side (Fig. 1). These extruded bases may be sites for DNA modification.