Structural basis of DNA folding and recognition in an AMP-DNA aptamer complex: distinct architectures but common recognition motifs for DNA and RNA aptamers complexed to AMP
Structural basis of DNA folding and recognition in an AMP-DNA aptamer complex: distinct architectures but common recognition motifs for DNA and RNA aptamers complexed to AMP
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DOI：
10.1016/s1074-5521(97)90115-0
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发表时间：
1997-11-01
影响因子：
--
通讯作者：
Patel, DJ
中科院分区：
文献类型：
--
作者：
Lin, CH;Patel, DJ
背景：通过体外筛选和扩增鉴定的RNA和DNA适体复合物的核磁共振（NMR）结构研究为RNA和DNA三级结构和溶液中的分子识别提供了丰富的信息，具有微摩尔亲和力的靶向ATP（和AMP）的RNA和DNA适体具有不同的结合位点序列和二级结构。我们在下面报道溶液中AMP-DNA适体复合物的三级结构，并将其与先前报道的溶液中AMP-RNA适体复合物的三级结构进行比较。结果：AMP- dna适体复合物的溶液结构显示，令人惊讶的是，两个AMP分子嵌入在矩形加宽的小凹槽内的相邻位置。复合体的形成涉及自适应结合，其中自由DNA适体的不对称内部气泡通过形成连续的六碱基错配片段而拉上，其中包括一对相邻的三碱基平台。AMP分子通过沃森-克里克边缘与鸟嘌呤残基的凹槽边缘配对，这些识别G.A错配的两侧是剪切的G.A和反向的Hoogsteen G.G错配对。结论：AMP-DNA适体和AMP-RNA适体复合物具有不同的三级结构和结合化学计量学。然而，这两个复合物在其结合袋中具有相似的结构特征和识别对齐。具体而言，AMP通过插入嘌呤碱基和通过相同的G.A错配形成来靶向DNA和RNA适配体。在两个复合物中，识别G.A错配在一个方向上与反向Hoogsteen G.G错配叠加，在另一个方向上与腺嘌呤碱基叠加。令人惊讶的是，在每种情况下，从10（14）个分子文库中独立选择的DNA和RNA适配体利用相同的错配比对，在含有共同结构元件的结合位点口袋中进行具有微摩尔亲和力的分子识别。
Background: Structural studies by nuclear magnetic resonance (NMR) of RNA and DNA aptamer complexes identified through in vitro selection and amplification have provided a wealth of information on RNA and DNA tertiary structure and molecular recognition in solution, The RNA and DNA aptamers that target ATP (and AMP) with micromolar affinity exhibit distinct binding site sequences and secondary structures. We report below on the tertiary structure of the AMP-DNA aptamer complex in solution and compare it with the previously reported tertiary structure of the AMP-RNA aptamer complex in solution.Results: The solution structure of the AMP-DNA aptamer complex shows, surprisingly, that two AMP molecules are intercalated at adjacent sites within a rectangular widened minor groove. Complex formation involves adaptive binding where the asymmetric internal bubble of the free DNA aptamer zippers up through formation of a continuous six-base mismatch segment which includes a pair of adjacent three-base platforms. The AMP molecules pair through their Watson-Crick edges with the minor groove edges of guanine residues, These recognition G.A mismatches are flanked by sheared G.A and reversed Hoogsteen G.G mismatch pairs.Conclusions: The AMP-DNA aptamer and AMP-RNA aptamer complexes have distinct tertiary structures and binding stoichiometries. Nevertheless, both complexes have similar structural features and recognition alignments in their binding pockets, Specifically, AMP targets both DNA and RNA aptamers by intercalating between purine bases and through identical G.A mismatch formation, The recognition G.A mismatch stacks with a reversed Hoogsteen G.G mismatch in one direction and with an adenine base in the other direction in both complexes, It is striking that DNA and RNA aptamers selected independently from libraries of 10(14) molecules in each case utilize identical mismatch alignments for molecular recognition with micromolar affinity within binding-site pockets containing common structural elements.