Hydration of Watson-Crick Base Pairs and Dehydration of Hoogsteen Base Pairs Inducing Structural Polymorphism under Molecular Crowding Conditions
Hydration of Watson-Crick Base Pairs and Dehydration of Hoogsteen Base Pairs Inducing Structural Polymorphism under Molecular Crowding Conditions
复制标题
DOI：
10.1021/ja805972a
复制
发表时间：
2009-03-18
影响因子：
15
通讯作者：
Sugimoto, Naoki
中科院分区：
文献类型：
--
作者：
Miyoshi, Daisuke;Nakamura, Kaori;Sugimoto, Naoki
最近已经揭示，分子拥挤是体内和体外条件之间的最大差异之一，是决定核酸的结构、稳定性和功能的关键因素。然而，分子拥挤对沃森-克里克和Hoogsteen碱基对的影响仍然不清楚。为了直接和定量地研究核酸中碱基对类型的分子拥挤效应，我们设计了分别由Hoogsteen和Watson-Crick碱基对组成的分子内平行链和反平行链DNA双链体，以及含有两种类型碱基对的分子内平行链三链体。热力学分析表明，在25 ℃下，Hoogsteen碱基对形成的自由能变化值在分子内双链体和三链体中分别从+ 1.45 +/- 0.15降至+ 1.09 +/- 0.13 kcal mol（-1）和从-1.89 +/- 0.13降至-2.71 +/- 0.11 kcal mol（-1），当PEG 200（平均分子量为200的聚乙二醇）的浓度从0增加到20wt%时，然而，双链体和三链体中沃森-克里克形成的相应值分别从-10.2 +/- 0.2增加到-8.7 +/- 0.1 kcal mol（-1）和从-10.8 +/- 0.2增加到-9.2 +/- 0.2 kcal mol-1。此外，还揭示了Hoogsteen和Watson-Crick碱基对上分子拥挤的相反效应是由于水分子与DNA链结合的不同行为。
It has been revealed recently that molecular crowding, which is one of the largest differences between in vivo and in vitro conditions, is a critical factor determining the structure, stability, and function of nucleic acids. However, the effects of molecular crowding on Watson-Crick and Hoogsteen base pairs remain unclear. In order to investigate directly and quantitatively the molecular crowding effects on base pair types in nucleic acids, we designed intramolecular parallel- and anti parallel -stranded DNA duplexes consisting of Hoogsteen and Watson-Crick base pairs, respectively, as well as an intramolecular parallel-stranded triplex containing both types of base pairs. Thermodynamic analyses demonstrated that the values of free energy change at 25 degrees C for Hoogsteen base-pair formations decreased from + 1.45 +/- 0.15 to + 1.09 +/- 0.13 kcal mol(-1), and from -1.89 +/- 0.13 to -2.71 +/- 0.11 kcal mol(-1) in the intramolecular duplex and triplex, respectively, when the concentration of PEG 200 (polyethylene glycol with average molecular weight 200) increased from 0 to 20 wt %. However, corresponding values for Watson-Crick formation in the duplex and triplex increased from -10.2 +/- 0.2 to -8.7 +/- 0.1 kcal mol(-1), and from -10.8 +/- 0.2 to -9.2 +/- 0.2 kcal mol-1, respectively. Furthermore, it was revealed that the opposing effects of molecular crowding on the Hoogsteen and Watson-Crick base pairs were due to different behaviors of water molecules binding to the DNA strands.