Structures of the ISWI-nucleosome complex reveal a conserved mechanism of chromatin remodeling
Structures of the ISWI-nucleosome complex reveal a conserved mechanism of chromatin remodeling
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ISWI-核小体复合物的结构揭示了染色质重塑的保守机制
DOI：
10.1038/s41594-019-0199-9
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发表时间：
2019-04-01
影响因子：
16.8
通讯作者：
Chen, Zhucheng
中科院分区：
文献类型：
--
作者：
Yan, Lijuan;Wu, Hao;Chen, Zhucheng
染色质重塑是不同的酶，已经提出了不同的模型来解释这些蛋白质如何工作。在这里，我们报告的3.3 A-分辨率低温电子显微镜（cryo-EM）结构的酿酒酵母ISWI（ISW 1）在复杂的核小体在腺苷二磷酸（ADP）结合和ADP-BeFx结合状态。数据显示，在核小体结合后，ISW 1通过催化结构域的大量重排而被激活，其中调节AutoN结构域包装第一个RecA样核心，NegC结构域被无序化。高分辨率结构揭示了ADP结合状态下ISW 1诱导的局部DNA畸变和易位，这与Snf 2染色质重塑剂诱导的DNA畸变和易位基本相同，表明DNA易位的共同机制。组蛋白核心在很大程度上保持不受干扰，通过交联防止组蛋白变形并没有抑制酵母ISW 1或其人类同源物的活性。总之，我们的研究结果表明，染色质重塑的一般机制涉及局部DNA畸变，而没有显着的组蛋白变形。
Chromatin remodelers are diverse enzymes, and different models have been proposed to explain how these proteins work. Here we report the 3.3 A-resolution cryogenic electron microscopy (cryo-EM) structures of Saccharomyces cerevisiae ISWI (ISW1) in complex with the nucleosome in adenosine diphosphate (ADP)-bound and ADP-BeFx-bound states. The data show that after nucleosome binding, ISW1 is activated by substantial rearrangement of the catalytic domains, with the regulatory AutoN domain packing the first RecA-like core and the NegC domain being disordered. The high-resolution structure reveals local DNA distortion and translocation induced by ISW1 in the ADP-bound state, which is essentially identical to that induced by the Snf2 chromatin remodeler, suggesting a common mechanism of DNA translocation. The histone core remains largely unperturbed, and prevention of histone distortion by crosslinking did not inhibit the activity of yeast ISW1 or its human homolog. Together, our findings suggest a general mechanism of chromatin remodeling involving local DNA distortion without notable histone deformation.