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通过ISWI在活性ATP水解过程中重塑染色体的结构见解

Youyang Sia^1,2,3,4, Han Pan^1,2,3,4, Kangjing Chen^1,2,3,4

¹MOE Key Laboratory of Protein Science, Tsinghua University, Beijing, P. R. China.

Science (New York, N.Y.)

|April 3, 2025

概括

像模拟开关 (ISWI) 这样的染色体重塑器使用ATP水解来移动核体. 这项研究显示ISWI

科学领域:

分子生物学
结构生物学
表观遗传学

背景情况:

染色体重塑器是使用腺三酸盐 (ATP) 水解来改变核细胞结构的基本分子机器.
这些重塑剂在调节DNA可访问性,基因表达和其他DNA模板过程中发挥着关键作用.
模拟开关 (ISWI) 改造器家族对于保持色素组织和功能至关重要.

研究的目的:

阐明ISWI染色体重塑剂的腺三酶 (ATPase) 循环的结构机制.
了解ISWI如何在ATP水解和DNA转移过程中与核细胞相互作用.
确定管理ISWI改造活动的监管要素.

主要方法:

在ATPase循环的各个阶段使用X射线结晶学来确定ISWI与核细胞结合的结构.
结构数据的分析捕获了ISWI运动领域的形状变化.
在重塑复合体内对DNA扭曲和基因组核酶相互作用的研究.

主要成果:

结构显示ISWI在整个ATPase循环中的不同构造,包括活性水解和重塑的状态.
在ADP*和apo*状态的ISWI结合部位观察到显著的DNA扭曲,包括基对膨胀和组织蛋白接触的丧失.
在脱离重塑循环的酶构成中发现了一种新的链接器DNA感应制动机制.

结论:

这些发现支持ISWI染色体重塑的多态模型.
通过ISWI阐明了DNA转移和调节的综合机制.
结构洞察力为了解染色体重塑如何影响基因调节提供了基础.

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