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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structural basis of photosensitivity in a bacterial light-oxygen-voltage/helix-turn-helix (LOV-HTH) DNA-binding protein
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Structural basis of photosensitivity in a bacterial light-oxygen-voltage/helix-turn-helix (LOV-HTH) DNA-binding protein

机译:细菌光-氧-电压/螺旋-转-螺旋(LOV-HTH)DNA结合蛋白中光敏性的结构基础

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摘要

Light-oxygen-voltage (LOV) domains are blue light-activated signaling modules integral to a wide range of photosensory proteins. Upon illumination, LOV domains form internal protein-flavin ad-ducts that generate conformational changes which control effector function. Here we advance our understanding of LOV regulation with structural, biophysical, and biochemical studies of EL222, a light-regulated DNA-binding protein. The dark-state crystal structure reveals interactions between the EL222 LOV and helix-turn-helix domains that we show inhibit DNA binding. Solution biophysical data indicate that illumination breaks these interactions, freeing the LOV and helix-turn-heiix domains of each other. This - conformational change has a key functional effect allowing EL222 to bind DNA in a light-dependent manner. Our data reveal a conserved signaling mechanism among diverse LOV-containing proteins, where light-induced conformational changes trigger activation via a conserved interaction surface.
机译:光氧电压(LOV)域是蓝色光激活的信号传导模块,是多种光感蛋白的组成部分。光照后,LOV结构域形成内部蛋白黄素加合物,后者产生控制效应子功能的构象变化。在这里,我们通过对光调节的DNA结合蛋白EL222的结构,生物物理和生化研究来提高对LOV调节的了解。暗态晶体结构揭示了EL222 LOV与我们显示抑制DNA结合的螺旋-转-螺旋结构域之间的相互作用。溶液的生物物理数据表明,光照破坏了这些相互作用,使LOV和螺旋-转-heiix域彼此释放。这种构象变化具有关键的功能作用,允许EL222以光依赖的方式结合DNA。我们的数据揭示了多种包含LOV的蛋白质之间的保守信号传导机制,其中光诱导的构象变化通过保守的相互作用表面触发激活。

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  • 作者单位

    Departments of Biochemistry and Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8816;

    Center for Biomembrane Systems, Department of Molecular Biology and Biochemistry, Department of Physiology and Biophysics, Department of Information and Computer Science, University of California, Irvine, CA 92697-3900;

    Center for Biomembrane Systems, Department of Molecular Biology and Biochemistry, Department of Physiology and Biophysics, Department of Information and Computer Science, University of California, Irvine, CA 92697-3900;

    Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064,Early Stage Pharmaceutical Development, Genentech, Inc., South San Francisco, CA 94080;

    Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064;

    Center for Biomembrane Systems, Department of Molecular Biology and Biochemistry, Department of Physiology and Biophysics, Department of Information and Computer Science, University of California, Irvine, CA 92697-3900;

    Departments of Biochemistry and Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8816;

  • 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

    allosteric regulation; photosensing; PER-ARNT-SIM domain;

    机译:变构调节光敏;PER-ARNT-SIM网域;

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