Structure and stability of higher-order human telomeric quadruplexes.
Structure and stability of higher-order human telomeric quadruplexes.
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高阶人端粒四链体的结构和稳定性。
DOI：
10.1021/ja209192a
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发表时间：
2011-12-28
影响因子：
15
通讯作者：
Chaires, Jonathan B.
中科院分区：
文献类型：
--
作者：
Petraccone, Luigi;Spink, Charles;Trent, John O.;Garbett, Nichola C.;Mekmaysy, Chongkham S.;Giancola, Concetta;Chaires, Jonathan B.
使用圆二色性、沉降速度、差示扫描量热法和分子动力学模拟研究了序列 5'-(TTAGGG)n 和 5'(TTAGGG)nTT (n=4,8,12) 中 G-四链体的形成。包含 8 和 12 个重复的序列分别形成具有两个和三个连续四链体的高阶结构。这些序列的合理结构是通过分子动力学模拟确定的，然后通过沉降速度对预测的流体动力学特性进行实验测试。这些结构的特点是链折叠成具有混合杂化构象的连续四链体。热力学研究表明，链自发折叠以包含最大数量的连续四链体。对于序列 5'(TTAGGG)12TT，超过 90% 的链包含具有三个四链体的完全折叠结构。三个四联体结构的基于统计力学的热分析图的反卷积表明，每个四联体都以独特的热力学参数独立熔化。热力学分析进一步表明，高阶结构中的四联体相对于其单体对应物来说不稳定，具有不利的耦合自由能。因此，四链体稳定性关键取决于序列和结构背景。
G-quadruplex formation in the sequences 5′-(TTAGGG)n and 5′(TTAGGG)nTT (n=4,8,12) was studied using circular dichroism, sedimentation velocity, differential scanning calorimetry and molecular dynamics simulations. Sequences containing 8 and 12 repeats formed higher-order structures with two and three contiguous quadruplexes, respectively. Plausible structures for these sequences were determined by molecular dynamics simulations followed by experimental testing of predicted hydrodynamic properties by sedimentation velocity. These structures featured folding of the strand into contiguous quadruplexes with mixed hybrid conformations. Thermodynamic studies showed the strands folded spontaneous to contain the maximum number contiguous quadruplexes. For the sequence 5′(TTAGGG)12TT, more than 90% of the strands contained completely folded structures with three quadruplexes. Statistical mechanical-based deconvolution of thermograms for three quadruplex structures showed that each quadruplex melted independently with unique thermodynamic parmameters. Thermodynamic analysis revealed further that quadruplexes in higher-ordered structures were destabilized relative to their monomeric counterparts, with unfavorable coupling free energies. Quadruplex stability thus depends critically on the sequence and structural context.
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G-四链体配体与人染色体末端的优先结合。
影响因子：
14.9
作者：
Granotier, C;Pennarun, G;Riou, L;Hoffschir, F;Gauthier, LR;De Cian, A;Gomez, D;Mandine, E;Riou, JF;Mergny, JL;Mailliet, P;Dutrillaux, B;Boussin, FD
通讯作者：
Boussin, FD
影响因子：
2
作者：
Gray, Donald M.;Wen, Jin-Der;Fleischhauer, Joerg
通讯作者：
Fleischhauer, Joerg
影响因子：
3.4
作者：
Degtyareva, Natalya N.;Wallace, Bret D.;Petty, Jeffrey T.
通讯作者：
Petty, Jeffrey T.
影响因子：
2.9
作者：
Antonacci, Cosimo;Chaires, Jonathan B.;Sheardy, Richard D.
通讯作者：
Sheardy, Richard D.
影响因子：
2.9
作者：
Bauer, Lubos;Tluckova, Katarina;Viglasky, Viktor
通讯作者：
Viglasky, Viktor