The solution structure of d(G4T4G3)2:: a bimolecular G-quadruplex with a novel fold
The solution structure of d(G4T4G3)2:: a bimolecular G-quadruplex with a novel fold
复制标题
DOI：
10.1016/s0022-2836(02)00569-7
复制
发表时间：
2002-07-26
影响因子：
5.6
通讯作者：
Plavec, J
中科院分区：
文献类型：
--
作者：
Crnugelj, M;Hud, NV;Plavec, J
富含G的11聚体寡核苷酸d（G（4）T（4）G（3））在钠离子存在下形成双分子G-四链体，其拓扑结构不同于密切相关且充分表征的序列d（G（4）T（4）G（4））和d（G（3）T（4）G（3））的折叠。用核磁共振谱和约束分子动力学计算相结合的方法确定了d（G（4）T（4）G（3））（2）的溶液结构. d（G（4）T（4）G（3））（2）形成由三个堆叠的G-四联体组成的不对称二聚体折回结构。两个T-4环对角地横跨G-四联体的外表面，呈现不同的构象。鸟嘌呤碱基的糖苷扭转角构象在一条链中为5 '-syn-anti-syn-anti-（T-4环）-anti-syn-anti，在另一条链中为5'-syn-anti-syn-anti-（T-4环）-syn-anti-syn。两个外G-四联体的鸟嘌呤碱基呈现顺时针的给体-受体氢键方向性，而中间G-四联体的鸟嘌呤碱基呈现逆时针的方向性。这种G-四链体的拓扑结构，像其他双分子折叠结构与对角环，放置G-四链体区域的每条链旁边的相邻的平行和反平行链。不参与G-四联体形成的两个鸟嘌呤残基G4和G12（即一条链的第四个鸟嘌呤碱基和另一条链的第一个鸟嘌呤碱基）采用不同的构象。G4堆叠在相邻G-四联体的顶部，并且这种碱基堆叠沿着环残基T5和T6的碱基继续。G12的方向远离G-四联体的核心;堆叠在T7碱基上，显然与同一残基的磷酸二酯基团发生氢键相互作用。d（G（4）T（4）G（3））（2）四链体结构的阳离子依赖性折叠与在类似序列中观察到的不同。虽然d（G（4）T（4）G（4））和d（G（3）T（4）G（3））在Na+、K+和NH 4+存在下形成双分子、对角环状的G-四链体结构，但我们观察到这种折叠有利于d（G（4）T（4）G（3））在Na+存在下，而不是在K+或NH 4+存在下。d（G（4）T（4）G（3））（2）的结构显示出一个“滑动环”元件，该元件类似于一些G-四链体折叠途径中的结构中间体，因此为这些提出的G-四链体形成中的瞬时结构的可行性提供了支持。(C)2002年由Elsevier Science Ltd.出版
The G-rich 11-mer oligonucleotide d(G(4)T(4)G(3)) forms a bimolecular G-quadruplex in the presence of sodium ions with a topology that is distinct from the folds of the closely related and well-characterized sequences d(G(4)T(4)G(4)) and d(G(3)T(4)G(3)). The solution structure of d(G(4)T(4)G(3))(2) has been determined using a combination of NMR spectroscopy and restrained molecular dynamics calculations. d(G(4)T(4)G(3))(2) forms an asymmetric dimeric fold-back structure consisting of three stacked G-quartets. The two T-4 loops that span diagonally across the outer faces of the G-quartets assume different conformations. The glycosidic torsion angle conformations of the guanine bases are 5'-syn-anti-syn-anti-(T-4 loop)-anti-syn-anti in one strand and 5'-syn-anti-syn-anti-(T-4 loop)-syn-anti-syn in the other strand. The guanine bases of the two outer G-quartets exhibit a clockwise donor-acceptor hydrogen-bonding directionality, while those of the middle G-quartet exhibit the anti-clockwise directionality. The topology of this G-quadruplex, like other bimolecular fold-back structures with diagonal loops, places each strand of the G-quartet region next to a neighboring parallel and an anti-parallel strand. The two guanine residues not involved in G-quartet formation, G4 and G12 (i.e. the fourth guanine base of one strand and the first guanine base of the other strand), adopt distinct conformations. G4 is stacked on top of an adjacent G-quartet, and this base-stacking continues along with the bases of the loop residues T5 and T6. G12 is orientated away from the core of G-quartets; stacked on the T7 base and apparently involved in hydrogen-bonding interactions with the phosphodiester group of this same-residue. The cation-dependent folding of the d(G(4)T(4)G(3))(2) quadruplex structure is distinct from that observed for similar sequences. While both d(G(4)T(4)G(4),) and d(G(3)T(4)G(3)) form bimolecular, diagonally looped G-quadruplex structures in the presence of Na+, K+ and NH4+,we have observed this folding to be favored for d(G(4)T(4)G(3)) in the presence of Na+, but not in the presence of K+ or NH4+. The structure of d(G(4)T(4)G(3))(2) exhibits a "slipped-loop" element that is similar to what has been proposed for structural intermediates in the folding pathway of some G-quadruplexes, and therefore provides support for the feasibility of these proposed transient structures in G-quadruplex formation. (C) 2002 Published by Elsevier Science Ltd.