DNA Minor Groove Sensing and Widening by the CCAAT-Binding Complex
DNA Minor Groove Sensing and Widening by the CCAAT-Binding Complex
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DOI：
10.1016/j.str.2012.07.012
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发表时间：
2012-10-10
期刊：
影响因子：
5.7
通讯作者：
Brakhage, Axel A.
中科院分区：
文献类型：
--
作者：
Huber, Eva M.;Scharf, Daniel H.;Brakhage, Axel A.
CCAAT盒是真核启动子的常见元件，其被保守的异三聚体CCAAT结合复合物(CBC)的特异性识别构成了启动子组织和转录调节的关键步骤。在这里，我们以 1.8 埃的分辨率报告了构巢曲霉 CBC 在不存在双链 DNA 以及与双链 DNA 复合的情况下的晶体结构。组蛋白样亚基 HapC 和 HapE 通过与糖磷酸骨架相互作用诱导核小体样 DNA 弯曲。如结构和生化数据所示，HapB 亚基的小沟感应和加宽将 CBC 紧紧锚定到 CCAAT 盒上。此外，DNA 双链体与 HapB 亚基的重要相互作用为 CBC 的序列特异性提供了解释。本文描述的转录因子结合模式回答了组蛋白如何获得 CCAAT 盒序列特异性的问题。
The CCAAT box is a frequent element of eukaryotic promoters, and its specific recognition by the conserved heterotrimeric CCAAT-binding complex (CBC) constitutes a key step in promoter organization and regulation of transcription. Here, we report the crystal structures of the CBC from Aspergillus nidulans in the absence and in complex with double-stranded DNA at 1.8 angstrom resolution. The histone-like subunits HapC and HapE induce nucleosome-like DNA bending by interacting with the sugar-phosphate backbone. Minor groove sensing and widening by subunit HapB tightly anchor the CBC to the CCAAT box, as shown by structural and biochemical data. Furthermore, crucial interactions of the DNA duplex with subunit HapB provide an explanation for the sequence specificity of the CBC. The herein-described mode of transcription factor binding answers the question of how histone proteins gained sequence specificity for the CCAAT box.