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The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes

机译:染色质重塑剂ACF充当空间核小体的二聚体马达

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摘要

Evenly spaced nucleosomes directly correlate with condensed chromatin and gene silencing. The ATP-dependent chromatin assembly factor (ACF) forms such structures in vitro and is required for silencing in vivo. ACF generates and maintains nucleosome spacing by constantly moving a nucleosome towards the longer flanking DNA faster than the shorter flanking DNA. How the enzyme rapidly moves back and forth between both sides of a nucleosome to accomplish bidirectional movement is unknown. Here we show that nucleosome movement depends cooperatively on two ACF molecules, indicating that ACF functions as a dimer of ATPases. Further, the nucleotide state determines whether the dimer closely engages one or both sides of the nucleosome. Three-dimensional reconstruction by single-particle electron microscopy of the ATPase-nucleosome complex in an activated ATP state reveals a dimer architecture in which the two ATPases face each other. Our results indicate a model in which the two ATPases work in a coordinated manner, taking turns to engage either side of a nucleosome, thereby allowing processive bidirectional movement. This novel dimeric motor mechanism differs from that of dimeric motors such as kinesin and dimeric helicases that processively translocate unidirectionally and reflects the unique challenges faced by motors that move nucleosomes.
机译:间隔均匀的核小体与浓缩的染色质和基因沉默直接相关。 ATP依赖的染色质装配因子(ACF)在体外形成这种结构,是体内沉默所必需的。 ACF通过不断地使核小体比较短的侧翼DNA更快地移向较长的侧翼DNA,来生成并保持核小体的间隔。酶如何在核小体的两侧之间快速来回移动以完成双向移动尚不清楚。在这里,我们显示核小体的运动合作取决于两个ACF分子,表明ACF充当ATPase的二聚体。此外,核苷酸状态决定了二聚体是否紧密地与核小体的一侧或两侧接合。通过单粒子电子显微镜对处于激活ATP状态的ATPase-核小体复合物进行三维重建,揭示了其中两个ATPase彼此面对的二聚体结构。我们的结果表明了一个模型,其中两个ATPase以协调的方式工作,轮流接合核小体的任一侧,从而允许进行性的双向运动。这种新颖的二聚体马达机制不同于驱动力和二聚体解旋酶之类的二聚体马达,所述二聚体马达单向性地单向转移并反映了移动核小体的马达所面临的独特挑战。

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  • 来源
    《Nature》 |2009年第7276期|1016-1021|共6页
  • 作者单位

    Department of Biochemistry and Biophysics, University of California, 600 16th Street;

    Department of Biochemistry and Biophysics, University of California, 600 16th Street;

    Department of Biochemistry and Biophysics, University of California, 600 16th Street;

    Department of Biochemistry and Biophysics, University of California, 600 16th Street;

    Department of Biochemistry and Biophysics, University of California, 600 16th Street;

    Department of Biochemistry and Biophysics, University of California, 600 16th Street;

    Department of Biochemistry and Biophysics, University of California, 600 16th Street;

    Department of Biochemistry and Biophysics, University of California, 600 16th Street The W.M. Keck Advanced Microscopy Laboratory, Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California 94158, USA;

    Department of Biochemistry and Biophysics, University of California, 600 16th Street;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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