• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >How NF-kappaB can be attracted by its cognate DNA.
【24h】

How NF-kappaB can be attracted by its cognate DNA.

机译：NF-kappaB如何被其同源DNA吸引。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

NF-kappaB is involved in the transcriptional regulation of a large number of genes, in particular those of human immunodeficiency virus (HIV). Recently, we used NMR spectroscopy and molecular modelling to study the solution structure of a native duplex related to the HIV-1 kappaB site, together with a mutated duplex for which a three base-pair change abolishes NF-kappaB binding. The native duplex shows unusual dynamics of the four steps surrounding the kappaB site. Here, we explore the intrinsic properties of the NMR-refined structures of both duplexes in order to understand why the native sequence is recognised by NF-kappaB among other DNA sequences. We establish that only the native kappaB site can adopt a conformation where its structure (curvature and base displacement), the accessibility and the electrostatic potentials of key atoms become very favourable for binding the large loops of NF-kappaB, in contrast to the mutated duplex. Finally, we show that the neutralisation of phosphate groups contacted by NF-kappaB favours a more canonical DNA structure. These findings lead to a new hypothesis for specific recognition through the phosphodiester backbone dynamics of the sequences flanking a binding site. Such unusual behaviour confers upon the overall duplex properties that can be used by NF-kappaB to select its binding site. Thus, the selectivity determinants for NF-kappaB binding appear to depend on deformability of an "extended" consensus sequence. Copyright 1999 Academic Press.
机译：NF-κB参与大量基因的转录调控，特别是人类免疫缺陷病毒（HIV）的基因。最近，我们使用NMR光谱和分子模型研究了与HIV-1 kappaB位点相关的天然双链体的溶液结构，以及一个突变的双链体，其三个碱基对的改变消除了NF-kappaB的结合。原生双链体显示了围绕kappaB位点的四个步骤的异常动态。在这里，我们探索了两个双链体的NMR精制结构的内在特性，以了解为什么天然序列被NF-kappaB识别为其他DNA序列。我们确定，只有天然kappaB位点可以采用其结构（曲率和碱基位移），关键原子的可及性和静电势变得非常适合结合NF-kappaB大环的构象，这与突变的双链体相反。最后，我们表明中和NF-κB接触的磷酸基团有利于更规范的DNA结构。这些发现导致通过结合位点两侧的序列的磷酸二酯主链动力学特异性识别的新假设。这种异常行为赋予了NF-κB可以用来选择其结合位点的整体双链体性质。因此，NF-κB结合的选择性决定簇似乎取决于“延伸的”共有序列的可变形性。版权所有1999，学术出版社。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号