Department of Biology, Johns Hopkins University, Baltimore, MD 21218-2685, USA.
J Mol Biol. 2010 Feb 19;396(2):431-40. doi: 10.1016/j.jmb.2009.11.050. Epub 2009 Nov 26.
The dimer formed by the ATF-2 and c-Jun transcription factors is one of the main components of the human interferon-beta enhanceosome. Although these two transcription factors are able to form two homodimers and one heterodimer, it is mainly the heterodimer that participates in the formation of this enhanceosome, binding specifically to the positive regulatory domain IV (PRDIV) site of the enhancer DNA. To understand this surprising advantage of the heterodimer, we investigated the association of these transcription factors using fragments containing the basic DNA-recognition segment and the basic leucine zipper domain (bZIP). It was found that the probability of forming the hetero-bZIP significantly exceeds the probability of forming homo-bZIPs, and that the hetero-bZIP interacts more strongly with the PRDIV site of the interferon-beta enhancer, especially in the orientation that places the folded ATF-2 basic segment in the upstream half of this asymmetric site. The effect of salt on the formation of the ATF-2/c-Jun dimer and on its ability to bind the target PRDIV site showed that electrostatic interactions between the charged groups of these proteins and with DNA play an essential role in the formation of the asymmetric ATF-2/c-Jun/PRDIV complex.
ATF-2 和 c-Jun 转录因子形成的二聚体是人类干扰素-β增强子的主要成分之一。尽管这两种转录因子能够形成两种同源二聚体和一种异源二聚体，但主要是异源二聚体参与了这种增强子的形成，特异性结合于增强子 DNA 的正调控区 IV（PRDIV）位点。为了理解这种异源二聚体的惊人优势，我们使用包含基本 DNA 识别片段和碱性亮氨酸拉链结构域（bZIP）的片段研究了这些转录因子的缔合。结果发现，形成异源 bZIP 的概率明显超过形成同源 bZIP 的概率，而且异源 bZIP 与干扰素-β增强子的 PRDIV 位点的相互作用更强，尤其是在将折叠的 ATF-2 碱性片段放置在该不对称位点的上游半部分的方向上。盐对 ATF-2/c-Jun 二聚体形成及其与靶 PRDIV 位点结合能力的影响表明，这些蛋白质的带电基团与 DNA 之间的静电相互作用在不对称 ATF-2/c-Jun/PRDIV 复合物的形成中起着至关重要的作用。
