Center for Integrated Protein Science, Department Chemie, Lehrstuhl für Biochemie, Technische Universität München, Garching 85747, Germany.
Structure. 2012 Oct 10;20(10):1757-68. doi: 10.1016/j.str.2012.07.012. Epub 2012 Aug 16.
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 Å 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.
CCAAT 框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) 特异性识别，这是启动子组织和转录调控的关键步骤。在这里，我们报道了来自构巢曲霉的 CBC 在无 DNA 和与双链 DNA 结合时的晶体结构，分辨率分别为 1.8Å 和 1.9Å。组蛋白样亚基 HapC 和 HapE 通过与糖-磷酸主链相互作用诱导核小体样 DNA 弯曲。亚基 HapB 通过对小沟的感应和加宽，将 CBC 紧密地锚定在 CCAAT 框上，结构和生化数据对此进行了证实。此外，DNA 双链与亚基 HapB 的关键相互作用为 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蛋白如何获得 CCAAT 框的序列特异性的问题。
