Volumetric Characterization of Sodium-Induced G-Quadruplex Formation
Volumetric Characterization of Sodium-Induced G-Quadruplex Formation
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DOI：
10.1021/ja110495c
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发表时间：
2011-03-30
影响因子：
15
通讯作者：
Chalikian, Tigran V.
中科院分区：
文献类型：
--
作者：
Fan, Helen Y.;Shek, Yuen Lai;Chalikian, Tigran V.
寡脱氧核糖核苷酸（ODN）与人类端粒序列的重复可以采取不同的四螺旋构象，表现出相似的能量参数。我们通过结合压力扰动量热法（PPC）、振动管密度法、超声测速法和高压下的UV熔融法研究了具有四个重复的人类端粒序列d[A（GGGTTA）（3）GGG]的ODN的折叠和未折叠状态的体积性质。我们进行了我们的体积测量在pH 7的水缓冲液中含有20，50和100 mM NaCl。所采用的所有方法都得到了非常一致的体积参数。导致形成折叠状态的构象转变的摩尔体积变化，Δ V是大的和正的。在50 mM NaCl下，在47 ℃的转变温度下，从所有方法获得的平均转变体积Δ V-tr为56.4 +/- 3.5 cm（3）mol（-1），Δ V-tr随着温度的升高而降低。我们进行了分子动力学模拟的ODN伴随四链体形成的内在几何参数的变化。根据实验和计算结果，ODN的折叠转变伴随着103 +/- 44个水分子从其水合壳释放到本体。这个数字对应于螺旋构象的净水合的18%。
Oligodeoxyribonucleotides (ODN) with repeats of the human telomeric sequence can adopt different tetrahelical conformations that exhibit similar energetic parameters. We studied the volumetric properties of the folded and unfolded states of an ODN with four repeats of the human telomeric sequence, d[A(GGGTTA)(3)GGG], by combining pressure-perturbation calorimetry (PPC), vibrating tube densimetry, ultrasonic velocimetry, and UV melting under high pressure. We carried out our volumetric measurements in aqueous buffers at pH 7 containing 20, 50, and 100 mM NaCl. All of the methods employed yielded volumetric parameters that were in excellent agreement. The molar volume changes, Delta V, of the conformational transition leading to formation of the folded state are large and positive. At 50 mM NaCl, the average transition volume, Delta V-tr, obtained from all the methods is 56.4 +/- 3.5 cm(3) mol(-1) at the transition temperature of 47 degrees C, with Delta V-tr decreasing with an increase in temperature. We carried out a molecular dynamics simulation of the change in the intrinsic geometric parameters of the ODN accompanying quadruplex formation. On the basis of the experimental and computational results, the folding transition of the ODN is accompanied by a release of 103 +/- 44 water molecules from its hydration shell to the bulk. This number corresponds to similar to 18% of the net hydration of the coil conformation.