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Structural mechanism of DNA- mediated NanogSox2 cooperative interaction

机译:DNA介导的纳米氧化物X2合作互动的结构机制

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摘要

The efficiency of stem cell transcriptional regulation always depends on the cooperative association and expression of transcription factors (TFs). Among these, Oct4, Sox2, and Nanog play major roles. Their cooperativity is facilitated via direct protein-protein interactions or DNA-mediated interactions, yet the mechanism is not clear. Most biochemical studies have examined Oct4/Sox2 cooperativity, whereas few studies have evaluated how Nanog competes in the connection between these TFs. In this study, using computational models and molecular dynamics simulations, we built a framework representing the DNA-mediated cooperative interaction between Nanog and Sox2 and analyzed the plausible interaction factors experienced by Nanog because of Sox2, its cooperative binding partner. Comparison of a wild-type and mutant Nanog/Sox2 model with the Nanog crystal structure revealed the regulatory structural mechanism between Nanog/Sox2-DNA-mediated cooperative bindings. Along with the transactivation domains interaction, the DNA-mediated allosteric interactions are also necessary for Nanog cooperative binding. DNA-mediated Nanog-Sox2 cooperativity influences the protein conformational changes and a stronger interaction profile was observed for Nanog-Mut (L103E) in comparison with the Nanog-WT complex.
机译:干细胞转录调节的效率总是取决于转录因子(TFS)的合作结合和表达。其中,OCT4,SOX2和Nanog发挥着重要作用。通过直接蛋白质 - 蛋白质相互作用或DNA介导的相互作用促进了它们的合作效应,但机制尚不清楚。大多数生化研究已经检查了Oct4 / Sox2合作,而少数研究已经评估Nanog在这些TF之间的连接中竞争。在这项研究中,使用计算模型和分子动力学模拟,我们建立了一种代表纳米和SOx2之间的DNA介导的合作相互作用的框架,并分析了纳米因SOX2,其合作结合伴侣的合理相互作用因子。野生型和突变纳米/ SOX2模型与纳米晶体结构的比较揭示了纳米/ SOX2-DNA介导的合作结合之间的调节结构机制。随着反膜激活结构域相互作用,DNA介导的颠覆相互作用也是纳米合作结合所必需的。与纳米-WT复合物相比,DNA介导的纳米Sox2合作影响纳米mut(L103E)观察到蛋白质构象变化和较强的相互作用谱。

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  • 来源
    《RSC Advances》 |2019年第14期|共10页
  • 作者单位

    Ajou Univ Dept Mol Sci &

    Technol Suwon 16499 South Korea;

    Ajou Univ Dept Mol Sci &

    Technol Suwon 16499 South Korea;

    Ajou Univ Dept Mol Sci &

    Technol Suwon 16499 South Korea;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
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