Bhavesh Neel S, Patel Prasanta K, Karthikeyan S, Hosur Ramakrishna V
Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400 005, India.
Biochem Biophys Res Commun. 2004 Apr 30;317(2):625-33. doi: 10.1016/j.bbrc.2004.03.095.
G-rich DNA has been known to form a variety of folded and multistranded structures, with even single base modifications causing important structural changes. But, very little is known about the dynamic characteristics of the structures, which may play crucial roles in facilitating the structural transitions. In this background, we report here NMR investigations on the structure and dynamics of a DNA repeat sequence GGCGGG in aqueous solution containing Na+ ions at neutral pH. The chosen sequence d-TGGCGGGT forms a parallel quadruplex with a C-tetrad in the middle, formed by symmetrical pairing of four Cs in a plane via NH2-O2 H-bonds. 13C relaxation measurements at natural abundance for C' sugar carbons provided valuable insight into the sequence specific dynamism of G and C-tetrads in the quadruplex. The C4 tetrad seems to introduce high conformational dynamism at milli- to micro-second time scale in the quadruplex. Concomitantly, there is a decrease in the pico-second time scale dynamics. Interestingly, these effects are seen more prominently at the G-tetrads on the 3' end of C-tetrad than on its 5' end. These observations would have important implications for the roles the tetrads may play in many biological functions.
富含鸟嘌呤的DNA已知会形成多种折叠和多链结构,即使是单个碱基修饰也会导致重要的结构变化。但是,对于这些结构的动态特征却知之甚少,而这些动态特征可能在促进结构转变中发挥关键作用。在此背景下,我们在此报告了在中性pH值含Na⁺离子的水溶液中对DNA重复序列GGCGGG的结构和动力学进行的核磁共振研究。所选序列d-TGGCGGGT形成了一个平行四链体,中间有一个C-四联体,由平面内四个C通过NH₂-O₂氢键对称配对形成。对C'糖碳的天然丰度进行¹³C弛豫测量,为四链体中G和C-四联体的序列特异性动态提供了有价值的见解。C4四联体似乎在毫秒到微秒的时间尺度上在四链体中引入了高构象动态性。同时,皮秒时间尺度的动力学有所下降。有趣的是,这些效应在C-四联体3'端的G-四联体上比在其5'端更为明显。这些观察结果对于四联体在许多生物学功能中可能发挥的作用具有重要意义。