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首页> 外文期刊>RSC Advances >Structural and conformational insights into SOX2/OCT4-bound enhancer DNA: a computational perspective
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Structural and conformational insights into SOX2/OCT4-bound enhancer DNA: a computational perspective

机译：对SOX2 / OCT4-结合的增强剂DNA的结构和构象见解：计算视角

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The potential role of sex determining region Y-box 2 (SOX2) and octamer-binding transcription factor 4 (OCT4) are increasingly discussed in stem cell maintenance either in the context of iPSCs (induced pluripotent stem cells) generation or cancer stem cell growth. These proteins bind to the enhancer and drive the transcription of a multitude of other factors that facilitate stem cell propagation. Here, we elucidated the mechanism of changes in DNA shape and the precise role of the interaction with the proteins, which is necessary to manipulate this ternary complex. Besides bending the DNA, SOX2 drove the DNA into the A-form, whereas OCT4 preferentially shaped DNA into a B-like conformation. SOX2 binding expanded the minor groove with simultaneous shrinkage of the major grove. Greater fluctuation in the DNA and bound proteins was observed after disruption of the protein–protein interaction. Dynamic cross-correlation of DNA atoms was found to be variable, and entropy of DNA atoms from DNA-wild-type-SOX2/OCT4 (DNA ~(WT) ) was the lowest among the various complexes. Moreover, essential dynamics-based conformational analysis revealed vivid conformational variation both in DNA alone and in protein bound complexes. Physical parameters such as the diffusion coefficient and dipole moment were also substantially different for DNA from the DNA ~(WT) complex. Taken together, our results establish a link between protein–protein and protein–DNA interactions, which will facilitate devising various strategies to modulate this complex in order to regulate the transcription of various proteins.
机译：性别测定区域Y型盒2（SOX2）和八辛er结合转录因子4（OCT4）的潜在作用在IPSC（诱导多能干细胞）产生或癌症干细胞生长的情况下，在干细胞维持中越来越多地讨论。这些蛋白质与增强剂结合并驱动促进干细胞繁殖的多种其他因素的转录。在这里，我们阐明了DNA形状的变化和与蛋白质相互作用的确切作用的机制，这对于操纵该三元复合物是必要的。除了弯曲DNA之外，SOX2将DNA驱动到A形，而OCT4优先地将DNA成B状构象。 SOX2绑定扩展了较小凹槽，具有主要的树丛的同时收缩。在破坏蛋白质 - 蛋白质相互作用后观察到DNA和结合蛋白质的更大波动。发现DNA原子的动态交叉相关是可变的，并且来自DNA - 野生型-SOX2 / OCT4（DNA〜（WT））的DNA原子的熵是各种配合物中最低的。此外，基于基于动态的构象分析显示了单独的DNA和蛋白质结合复合物的生动构象变化。来自DNA〜（WT）复合物的DNA的DNA也基本上不同的物理参数。我们的结果在一起建立了蛋白质 - 蛋白质和蛋白质-DNA相互作用之间的联系，这将有助于设计各种策略来调节该复合物，以调节各种蛋白质的转录。

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