Patel D J, Kozlowski S A, Suggs J W, Cox S D
Proc Natl Acad Sci U S A. 1981 Jul;78(7):4063-7. doi: 10.1073/pnas.78.7.4063.
We demonstrate that poly(dA-dT) can adopt two conformations in solution, with the relative proportions dependent on the nature and concentration of the counter ion and cationic ligands. The synthetic DNA exhibits a dinucleotide repeat conformation on addition of CsF and Me4NCl at molar concentrations, with the NMR spectral changes reflecting a common conformational change at one glycosidic torsion angle and one phosphodiester linkage. We also observe the same dinucleotide repeat in the neighbor-exclusion 3 alpha, 17 beta-dipyrrolidin-1'-yl-5 beta- delta 9,11-androstene dimethiodide (3 alpha, 5 beta, 17 beta-dipyrandenium) complex, with the steroid diammonium ligand binding in the groove of the stacked poly(dA-dT) duplex and the complex stabilized through the interaction of one of the charged ends with the backbone phosphate. We demonstrate further that 3 alpha, 5 beta, 17 beta-dipyrandenium bound to poly(dA-dT) at low binding ratios induces a switch to the dinucleotide repeat conformation at adjacent steroid-free duplex regions. This observation contrasts with a previous demonstration that the diastereoisomeric 3 beta, 5 alpha, 17 beta-dipyrandium binds to poly(dA-dT) by partial insertion between unstacked tilted base pairs. The NMR parameters rule out a left-handed alternating DNA structure (Z DNA) for the observed poly(dA-dT) dinucleotide repeat conformation, but right-handed alternating DNA models are under consideration. The facile interconversion of poly(dA-dT) between two conformations, one of which exhibits a dinucleotide repeat and can be induced by ligand binding, may provide a mechanism for the recognition of specific nucleic acid sequences by DNA-binding proteins.
我们证明，聚（dA-dT）在溶液中可呈现两种构象，其相对比例取决于抗衡离子和阳离子配体的性质及浓度。在加入摩尔浓度的CsF和Me4NCl时，合成DNA呈现二核苷酸重复构象，NMR光谱变化反映了一个糖苷扭转角和一个磷酸二酯键处常见的构象变化。我们还在邻位排斥的3α，17β - 二吡咯烷 - 1'-基 - 5β - Δ9,11 - 雄甾烯二甲碘化物（3α，5β，17β - 二吡咯烷鎓）复合物中观察到相同的二核苷酸重复，甾体二铵配体结合在堆积的聚（dA-dT）双链体的凹槽中，并且复合物通过一个带电末端与主链磷酸的相互作用而稳定。我们进一步证明，以低结合比与聚（dA-dT）结合的3α，5β，17β - 二吡咯烷鎓会在相邻的无甾体双链体区域诱导转变为二核苷酸重复构象。这一观察结果与先前的证明形成对比，即非对映异构体3β，5α，17β - 二吡咯烷鎓通过在未堆积的倾斜碱基对之间部分插入而与聚（dA-dT）结合。NMR参数排除了所观察到的聚（dA-dT）二核苷酸重复构象为左手交替DNA结构（Z-DNA），但右手交替DNA模型仍在考虑之中。聚（dA-dT）在两种构象之间的容易相互转化，其中一种呈现二核苷酸重复并且可由配体结合诱导，这可能为DNA结合蛋白识别特定核酸序列提供一种机制。
