A diamond-shaped zipper-like DNA architecture containing triads sandwiched between mismatches and tetrads
A diamond-shaped zipper-like DNA architecture containing triads sandwiched between mismatches and tetrads
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DOI：
10.1006/jmbi.1999.3345
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发表时间：
2000-01-21
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;Kettani, A;Patel, DJ
本文报道了富含鸟嘌呤和腺嘌呤的d（A（2）G（2）T（4）A（2）G（2））12-mer序列在中等NaCl溶液中形成独特折叠的溶液结构。该序列包含一对由T-4接头片段分隔的AAGG重复序列，其质子共振归属通过鸟嘌呤和腺嘌呤碱基的位点特异性N-15标记以及腺嘌呤的2，6-二氨基嘌呤和8-溴腺嘌呤，鸟嘌呤的8-溴鸟嘌呤，7-脱氮鸟嘌呤和肌苷以及胸腺嘧啶的尿嘧啶和5-溴尿嘧啶的位点特异性掺入来辅助。通过结合NMR和强度精细计算方法求解的溶液结构由通过一对d（A（2）G（2）T（4）A（2）G（2））发夹的二聚化形成的菱形结构组成。这种2重对称结构包含一个四链体核心，该核心由一对双链体相关的G（syn）. G（syn）.G（anti）.G（anti）四联体组成，其中相邻链具有平行和反平行的邻居，并连接形成对角环的T-4片段。每个G（syn）.G（syn）.G（anti）.G（anti）四联体形成一个平台，在其上堆叠一个T（anti）。[A（syn）-A（anti）]三联体，其含有新的A（syn）-A（anti）平台步骤和反向的Hoogsteen A（syn）.T（anti）对。我们观察到碱基-碱基和碱基-糖堆积相互作用，后者发生在剪切A-G步骤，其中A的糖堆积在G的嘌呤平面上。出乎意料的是，这个剪切的A（反）-G（顺）步骤的拓扑结构与左手Z-DNA中的C（反）-G（顺）步骤有许多相似之处。霸王(A-A)三联体夹在一侧的G-四分体和反向的Hoogsteen A（反）之间。T（反）对另一个。这种插入拓扑结构是由拉链样基序促进的，其中三联体的A（反）残基在拉伸的A（反）-G（顺）步骤内相互交叉。我们的结构研究报告了A-A平台、碱基三联体、拉链状交错和剪切碱基台阶的新方面，以及定义d（A（2），G（2）T（4）A（2）G（2））序列的钻石状结构的碱基-碱基和基糖堆叠。可以预期，混合的鸟嘌呤-腺嘌呤序列将表现出丰富多样的多态性结构，这将为核酸和蛋白质的识别提供独特的拓扑结构。(C)北京大学出版社.
The present study reports On the solution structure of the guanine plus adenine rich d(A(2)G(2)T(4)A(2)G(2)) 12-mer sequence which forms a unique fold in moderate NaCl solution. Proton resonance assignments for this sequence, which contains a pair of AAGG repeats separated by a T-4 linker segment, were aided by site-specific N-15-labeling of guanine and adenine bases, as well as site-specific incorporation of 2,6-diaminopurine and 8-bromoadenine for adenine, 8-bromoguanine, 7-deazaguanine and inosine for guanine, and uracil and 5-bromouracil for thymine. The solution structure, which was solved by a combined NMR and intensity-refined computational approach, consists of a diamond-shaped architecture formed through dimerization of a pair of d(A(2)G(2)T(4)A(2)G(2)) hairpins. This 2-fold symmetric structure contains a quadruplex core consisting of a pair of symmetry-related G(syn).G(syn).G(anti).G(anti) tetrads, where adjacent strands have both parallel and anti-parallel neighbors and connecting T-4 segments which form diagonal loops. Each of the G(syn).G(syn).G(anti).G(anti) tetrads forms a platform on which stacks a T(anti).[A(syn)-A(anti)] triad containing a novel A(syn)-A(anti) platform step and a reversed Hoogsteen A(syn).T(anti) pair. We observe both base-base and base-sugar stacking interactions, with the latter occuring at a sheared A-G step where the sugar of the A stacks on the purine plane of the G. Unexpectedly, the topology of this sheared A(anti)-G(syn) step has many similarities with the C(anti)-G(syn) step in left-handed Z-DNA. The T . (A-A) triad is sandwiched between the G-tetrad on one side and a reversed Hoogsteen A(anti) . T(anti) pair on the other. This intercalative topology is facilitated by a zipper-like motif where the A(anti) residue of the triad is interdigitated within a stretched A(anti)-G(syn) step. Our structural study reports on new aspects of A-A platforms, base triads, zipper-like interdigitation and sheared base steps, together with base-base and base-sugar stacking defining a diamond-like architecture for the d(A(2),G(2)T(4)A(2)G(2)) sequence. One can anticipate that mixed guanine-adenine sequences will exhibit a rich diversity of polymorphic architectures that will provide unique topologies for recognition by both nucleic acids and proteins. (C) 2000 Academic Press.