A double chain reversal loop and two diagonal loops define the architecture of a unimolecular DNA quadruplex containing a pair of stacked G(syn)•G(syn)•G(anti)•G(anti) tetrads flanked by a G•(T-T) triad and a T•T•T triple
A double chain reversal loop and two diagonal loops define the architecture of a unimolecular DNA quadruplex containing a pair of stacked G(syn)•G(syn)•G(anti)•G(anti) tetrads flanked by a G•(T-T) triad and a T•T•T triple
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DOI：
10.1006/jmbi.2001.4759
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发表时间：
2001-06-29
影响因子：
5.6
通讯作者：
Patel, DJ
中科院分区：
文献类型：
--
作者：
Kuryavyi, V;Majumdar, A;Patel, DJ
G（.）G（.）G（.）单价阳离子溶液中的G四联体排列的DNA四链体依赖于四条链的方向性，这反过来又由环连接性和鸟嘌呤顺/反分布沿着各条链和在各个G G G四联体内定义。最小的单分子G-四链体属于d（G（2）N（n）G（2）N（2）G（2）N（n）G（2））家族，它有可能形成两个通过N-n环连接的堆叠的G-四链体。以前的研究集中在凝血酶结合DNA适体d（G（2）T（2）G（2）TGTG（2）T（2）G（2）），其中第一和第三连接环的N-n为T-2，中间连接环的N-n为TGT。这种DNA适体在K+阳离子溶液中形成由两个堆叠的G（syn）（.）G（anti）（.）G（syn）（.）G（反）四分体，彼此反平行的相邻链，边缘连接T1，TGT和T1环。我们现在报告d（G（2）T（4）G（2）CAG（2）GT（4）G（2）T）序列的基于NMR的溶液结构，其与凝血酶结合DNA适体序列的不同之处在于具有较长的第一（T-4）和第三（GT（4））环以及较短的（CA）中间环。这种d（G（2）T（4）G（2）CAG（2）GT（4）G（2）T）序列在Na+阳离子溶液中形成由两个堆叠的G（syn）（.）G（syn）（.）G（anti）（.）G（反）四分体，相邻的链有一个平行和一个反平行的邻居和不同的非边向环连接。具体地，较长的第一（T-4）和第三（GT（4））环是对角型的，而较短的中间环是双链反转型的。此外，堆叠G（.）G（.）G（.）G四分体的一侧是G（T-T）三联体，另一侧是（TTT）-T-。T-。三倍。G（.）G（.）G（.）在先前报道的凝血酶结合DNA适体d（G（2）T（2）G（2）TGTG（2）T（2）G（2））四链体和本文报道的d（G（2）T（4）G（2）CAG（2）GT（2）G（2）T）四链体之间的G四链体加强了高阶DNA结构的多态性。此外，这两个小的单分子G-四链体，这是不同的彼此和平行链的G-四链体，提供了新的配体识别的目标。我们的研究结果表明，我们的实验室先前在四膜虫端粒d（T（2）G（4））（4）四链体中鉴定的双链反向环连接是一种稳健的折叠拓扑结构，因为它现在也在d（G（2）T（4）G（2）CAG（2）GT（2）G（2）T）四链体中观察到。G（.）(T-T)三和弦和（TTT）-T-.- T-。三重，扩展了对碱基三重体和三重体的可用识别比对。(C)北京：科学出版社.
The architecture of G(.)G(.)G(.)G tetrad-aligned DNA quadruplexes in monovalent cation solution is dependent on the directionality of the four strands, which in turn are defined by loop connectivities and the guanine syn/anti distribution along individual strands and within individual G G G G tetrads. The smallest unimolecular G-quadruplex belongs to the d(G(2)N(n)G(2)N(2)G(2)N(n)G(2)) family, which has the potential to form two stacked G-tetrads linked by N-n loop connectivities. Previous studies have focused on the thrombin-binding DNA aptamer d(G(2)T(2)G(2)TGTG(2)T(2)G(2)), where N-n was T-2 for the first and third connecting loops and TGT for the middle connecting loop. This DNA aptamer in K+ cation solution forms a unimolecular G-quadruplex stabilized by two stacked G(syn)(.)G(anti)(.)G(syn)(.)G(anti) tetrads, adjacent strands which are antiparallel to each other and edge-wise connecting T,, TGT and T,loops. We now report on the NMR-based solution structure of the d(G(2)T(4)G(2)CAG(2)GT(4)G(2)T) sequence, which differs from the thrombin-binding DNA aptamer sequence in having longer first (T-4) and third (GT(4)) loops and a shorter (CA) middle loop. This d(G(2)T(4)G(2)CAG(2)GT(4)G(2)T) sequence in Na+ cation solution forms a unimolecular G-quadruplex stabilized by two stacked G(syn)(.)G(syn)(.)G(anti)(.)G(anti) tetrads, adjacent strands which have one parallel and one antiparallel neighbors and distinct non-edge-wise loop connectivities. Specifically, the longer first (T-4) and third (GT(4)) loops are of the diagonal type while the shorter middle loop is of the double chain reversal type. In addition, the pair of stacked G(.)G(.)G(.)G tetrads are flanked on one side by a G (T-T) triad and on the other side by a (TTT)-T-.-T-. triple. The distinct differences in strand directionalities, loop connectivities and syn/anti distribution within G(.)G(.)G(.)G tetrads between the thrombin-binding DNA aptamer d(G(2)T(2)G(2)TGTG(2)T(2)G(2)) quadruplex reported previously, and the d(G(2)T(4)G(2)CAG(2)GT(2)G(2)T) quadruplex reported here, reinforces the polymorphic nature of higher-order DNA architectures. Further, these two small unimolecular G-quadruplexes, which are distinct from each other and from parallel-stranded G-quadruplexes, provide novel targets for ligand recognition. Our results demonstrate that the double chain reversal loop connectivity identified previously by our laboratory within the Tetrahymena telomere d(T(2)G(4))(4) quadruplex, is a robust folding topology, since it has now also been observed within the d(G(2)T(4)G(2)CAG(2)GT(2)G(2)T) quadruplex. The identification of a G(.)(T-T) triad and a (TTT)-T-.-T-. triple, expands on the available recognition alignments for base triads and triples. (C) 2001 Academic Press.