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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Visualization of the nanospring dynamics of the IkBα ankyrin repeat domain in real time
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Visualization of the nanospring dynamics of the IkBα ankyrin repeat domain in real time

机译：实时可视化IkBα锚蛋白重复域的纳米弹簧动力学

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摘要

IkBαis a crucial regulator of NFkB transcription. NFkB-mediated gene activation is robust because levels of free IkBα are kept extremely low by rapid, ubiquitin-independent degradation of newly synthesized licBa. IkBα has a weakly folded ankyrin repeat 5-6 (AR5-6) region that is critical in establishing its short intracel-lular half-life. The AR5-6 region of Ik-Bo folds upon binding to NFkB. The NFkB-bound IkBα has a long half-life and requires ubiquitin-targeted degradation. We present single molecule FRET evidence that the native state of IkBα transiently populates an intrinsically disordered state characterized by a more extended structure and fluctuations on the millisecond time scale. Binding to NFkB or introduction of stabilizing mutations in AR 6 suppressed the fluctuations, whereas higher temperature or small amounts of urea increased them. The results reveal that intrinsically disordered protein regions transition between collapsed and extended conformations under native conditions.
机译：IkBα是NFkB转录的关键调节因子。 NFkB介导的基因激活是强大的，因为通过新合成的licBa的快速，遍在蛋白非依赖性降解，游离IkBα的水平非常低。 IkBα具有弱折叠的锚蛋白重复序列​​5-6（AR5-6），这对于建立其较短的细胞内半衰期至关重要。当与NFkB结合时，Ik-Bo的AR5-6区域折叠。与NFkB结合的IkBα具有较长的半衰期，并且需要针对泛素的降解。我们目前的单分子FRET证据表明，IkBα的天然状态瞬时填充了固有的无序状态，其特征是结构的扩展性和毫秒级的波动。与NFkB结合或在AR 6中引入稳定突变抑制了波动，而较高温度或少量尿素则增加了波动。结果表明，在自然条件下，内在无序的蛋白质区域在塌陷和延伸构象之间转换。

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    Jorge A. Lamboy; Hajin Kim; Kyung Suk Lee; Taekjip Ha; Elizabeth A. Komives;

  • 作者单位

    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92092-0378;

    Department of Physics and Center for Physics in Living Cells, University of Illinois, Urbana-Champaign, Urbana, IL 61801-2902,Howard Hughes Medical Institute, University of Illinois, Urbana, IL 61801-2902;

    Department of Physics and Center for Physics in Living Cells, University of Illinois, Urbana-Champaign, Urbana, IL 61801-2902;

    Department of Physics and Center for Physics in Living Cells, University of Illinois, Urbana-Champaign, Urbana, IL 61801-2902,Howard Hughes Medical Institute, University of Illinois, Urbana, IL 61801-2902;

    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92092-0378;

  • 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

    intrinsically disordered protein; NFkappaB; transcription factor; protein dynamics;

    机译：内在无序的蛋白质NFκB;转录因子蛋白质动力学;

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