Madhumalar A, Bansal Manju
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
J Biomol Struct Dyn. 2005 Aug;23(1):13-27. doi: 10.1080/07391102.2005.10507043.
Deciphering sequence information from sugar-phosphate backbone is finely tuned through the conformational substates of DNA. BII conformation, one of the conformational substates of B-DNA, is known to play a key role in DNA-protein recognition. BI and BII are identified by the epsilon-zeta difference, which is negative in BI and positive in BII. Our analysis of MD and crystal structures shows that BII conformation is sequence specific and dinucleotides GC, CG, CA, TG, TA show high preference to take up BII conformation, while TT, TC, CT, CC dinucleotides rarely take up this conformation. Significant changes were observed in the dinucleotide parameters viz. twist, roll, and slide for the steps having BII conformation. Interestingly, the magnitude of variation in the dinucleotide parameters is seen to depend mainly on two factors, the magnitude of epsilon-zeta difference and the presence or absence of BII conformation in the second strand, across the WC base-paired dinucleotide step. Based on these two factors, the conformational substate of a dinucleotide step can be further classified as BI.BI (BI conformation in both strands), BI.BII (BI conformation in one strand and BII conformation in the other), and BII.BII (BII conformation in both strands). The occurrence of BII in both strands was found to be quite rare and thus, it can be concluded that BI.BI and BI.BII hybrid steps are more favorable than a BII.BII step. In conformity with the sequence preference seen for dinucleotides in each strand, BII.BII combination of backbone conformation was observed only for GC, CG, CA, and TG containing dinucleotide steps. We further classified BII.BII step as strong BII and weak BII depending on the magnitude of the average epsilon-zeta difference. The dinucleotide steps which belong to the category of strong BII, have large twist, high positive slide and negative roll values, while those in the weak BII group have roll, twist, and slide values similar to that of hybrid BI.BII steps. This conformational property could be contributing to the groove opening/closing and thus can modulate protein-DNA interaction.
通过DNA的构象亚态对来自糖磷酸骨架的序列信息进行精确解读。BII构象是B-DNA的构象亚态之一，已知在DNA-蛋白质识别中起关键作用。BI和BII通过ε-ζ差异来识别，该差异在BI中为负，在BII中为正。我们对分子动力学（MD）和晶体结构的分析表明，BII构象具有序列特异性，二核苷酸GC、CG、CA、TG、TA高度倾向于采取BII构象，而TT、TC、CT、CC二核苷酸很少采取这种构象。在具有BII构象的步移中，二核苷酸参数（即扭曲、滚动和滑动）发生了显著变化。有趣的是，二核苷酸参数的变化幅度主要取决于两个因素，即ε-ζ差异的大小以及在WC碱基配对的二核苷酸步移中第二条链中BII构象的有无。基于这两个因素，二核苷酸步移的构象亚态可进一步分为BI.BI（两条链均为BI构象）、BI.BII（一条链为BI构象，另一条链为BII构象）和BII.BII（两条链均为BII构象）。发现两条链中都出现BII的情况非常罕见，因此可以得出结论，BI.BI和BI.BII杂合步移比BII.BII步移更有利。与每条链中二核苷酸的序列偏好一致，仅在含有GC、CG、CA和TG的二核苷酸步移中观察到BII.BII主链构象组合。我们根据平均ε-ζ差异的大小将BII.BII步移进一步分为强BII和弱BII。属于强BII类别的二核苷酸步移具有大的扭曲、高的正滑动和负的滚动值，而弱BII组中的步移具有与杂合BI.BII步移相似的滚动、扭曲和滑动值。这种构象特性可能有助于沟槽的打开/关闭，从而可以调节蛋白质-DNA相互作用。
