...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Detection of a ternary complex of NF-κB and IκBα with DNA provides insights into how IκBα removes NF-κB from transcription sites
【24h】

Detection of a ternary complex of NF-κB and IκBα with DNA provides insights into how IκBα removes NF-κB from transcription sites

机译：用DNA检测NF-κB和IκBα的三元复合物可深入了解IκBα如何从转录位点去除NF-κB

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

It has been axiomatic in the field of NF-κB signaling that the formation of a stable complex between NF-κB and the ankyrin repeat protein IκBα precludes the interaction of NF-κB with DNA. Contradicting this assumption, we present stopped-flow fluorescence and NMR experiments that give unequivocal evidence for the presence of a ternary DNA-NF-κB-IκBα complex in solution. Stepwise addition of a DNA fragment containing the kB binding sequence to the IκBα-NF-κB complex results in changes in the IκBα NMR spectrum that are consistent with dissociation of the region rich in proline, glutamate, serine, and threonine (PEST) and C-terminal ankyrin repeat sequences of IκBα from the complex. However, even at high concentrations of DNA, IκBα remains associated with NF-κB, indicated by the absence of resonances of the free N-terminal ankyrin repeats of IκBα. The IκBα-mediated release of NF-κB from its DNA-bound state may be envisioned as the reverse of this process. The initial step would consist of the coupled folding and binding of the intrinsically disordered nuclear localization sequence of the p65 subunit of NF-κB to the well-structured N-terminal ankyrin repeats of IκBα. Subsequently the poorly folded C-terminal ankyrin repeats of IκBα would fold upon binding to the p50 and p65 dimerization domains of NF-κB, permitting the negatively charged C-terminal PEST sequence of IκBα to displace the bound DNA through a process of local mass action.
机译：在NF-κB信号传导领域中，公知的是，NF-κB和锚蛋白重复蛋白IκBα之间稳定的复合物的形成排除了NF-κB与DNA的相互作用。与这个假设相反，我们提出了停止流动的荧光和NMR实验，为溶液中存在三元DNA-NF-κB-IκBα复合物提供了明确的证据。向IκBα-NF-κB复合物中逐步添加包含kB结合序列的DNA片段会导致IκBαNMR谱的变化，这与富含脯氨酸，谷氨酸，丝氨酸和苏氨酸（PEST）和C的区域解离一致复合物中IκBα的末端锚蛋白重复序列​​。然而，即使在高浓度的DNA中，IκBα仍与NF-κB缔合，这由IκBα的游离N末端锚蛋白重复序列​​的共振缺失引起。 IκBα介导的NF-κB从其DNA结合状态的释放可能被认为是该过程的逆过程。第一步将包括折叠折叠和将NF-κBp65亚基的内在无序核定位序列与IκBα的结构良好的N末端锚蛋白重复序列​​结合。随后，折叠不佳的IκBα的C末端锚蛋白重复序列​​会与NF-κB的p50和p65二聚结构域结合而折叠，从而使IκBα的带负电荷的C末端PEST序列通过局部质量作用过程置换结合的DNA 。

著录项

  • 来源
  • 作者

    Shih-Che Sue; Vera Alverdi; Elizabeth A. Komives; H. Jane Dyson;

  • 作者单位

    Department of Molecular Biology MB2, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037-1000,Institute of Bioinformatics and Structural Biology, Department of Life Sciences, National Tsing Hua University, 101 Sec 2 Kuang Fu Road, Hsinchu 30013, Taiwan;

    Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92037-0378;

    Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92037-0378;

    Department of Molecular Biology MB2, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037-1000;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    signal transduction; transcription factor;

    机译：信号转导;转录因子;

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