Mechanism of chromatin remodelling revealed by the Snf2-nucleosome structure
Mechanism of chromatin remodelling revealed by the Snf2-nucleosome structure
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Snf2-核小体结构揭示染色质重塑机制
DOI：
10.1038/nature22036
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发表时间：
2017-04-27
期刊：
影响因子：
64.8
通讯作者：
Chen, Zhucheng
中科院分区：
文献类型：
--
作者：
Liu, Xiaoyu;Li, Meijing;Chen, Zhucheng
染色质重构体是一种类似解旋酶的、依赖于ATP的酶，它可以改变染色质的结构和核小体的位置，从而允许调节蛋白访问DNA。本文报道了与核小体结合的酿酒酵母染色质重塑开关/蔗糖非发酵型(SWI2/SNF2)的冷冻电子显微镜结构。结构表明，Snf2的两个核心区在核小体结合时重新排列，表明该酶被激活。核心区通过两个诱导的支撑链相互联系，这对连接ATP水解酶和染色质重塑至关重要。Snf2主要通过其主域裂隙内的解旋酶基序与核小体一个DNA环的磷酸盐骨架结合，暗示了不同重构体之间底物结合的保守机制。Snf2通过带正电荷的表面与第二个DNA环接触，提供了一种机制，将重构器锚定在核小体的固定位置。Snf2在结合部位局部使核小体DNA变形，为重塑反应准备底物。总而言之，这些发现为染色质的重塑提供了机械性的见解。
Chromatin remodellers are helicase-like, ATP-dependent enzymes that alter chromatin structure and nucleosome positions to allow regulatory proteins access to DNA. Here we report the cryo-electron microscopy structure of chromatin remodeller Switch/sucrose non-fermentable (SWI2/SNF2) fromSaccharomyces cerevisiaebound to the nucleosome. The structure shows that the two core domains of Snf2 are realigned upon nucleosome binding, suggesting activation of the enzyme. The core domains contact each other through two induced Brace helices, which are crucial for coupling ATP hydrolysis to chromatin remodelling. Snf2 binds to the phosphate backbones of one DNA gyre of the nucleosome mainly through its helicase motifs within the major domain cleft, suggesting a conserved mechanism of substrate engagement across different remodellers. Snf2 contacts the second DNA gyre via a positively charged surface, providing a mechanism to anchor the remodeller at a fixed position of the nucleosome. Snf2 locally deforms nucleosomal DNA at the site of binding, priming the substrate for the remodelling reaction. Together, these findings provide mechanistic insights into chromatin remodelling.