在这项工作中，课题组报告了在活性ATP水解和重塑过程中与核小体结合的模仿开关（ISWI）的结构，揭示了重塑马达在整个腺苷三磷酸酶（ATP酶）周期中的构象转变。DNA链相应地扭曲，显示出一个完整的碱基对凸起，并且在二磷酸腺苷* (ADP*)和载脂蛋白*（未结合）状态下，马达结合部位的组蛋白接触缺失。研究人员还确定了调节重塑活动的几个重要因素。值得注意的是，退出重塑周期的酶构象揭示了连接体DNA感应制动机制。总之，他们的发现阐明了ISWI作用的多状态模型，提供了支持染色质重塑的DNA易位和调控的综合机制。
据介绍，染色质重塑者利用三磷酸腺苷（ATP）水解的能量滑动核小体，调节细胞中的染色质结构和基因活性。
附：英文原文
Title: Structural insights into chromatin remodeling by ISWI during active ATP hydrolysis
Author: Youyang Sia, Han Pan, Kangjing Chen, Zhucheng Chen
Issue&Volume: 2025-06-05
Abstract: Chromatin remodelers utilize the energy of adenosine triphosphate (ATP) hydrolysis to slide nucleosomes, regulating chromatin structure and gene activity in cells. In this work, we report structures of imitation switch (ISWI) bound to the nucleosome during active ATP hydrolysis and remodeling, revealing conformational transitions of the remodeling motor across the adenosine triphosphatase (ATPase) cycle. The DNA strands were distorted accordingly, showing one full base-pair bulge and a loss of histone contact at the site of motor binding in the adenosine diphosphate* (ADP*) and apo* (unbound) states. We also identified several important elements for regulation of the remodeling activity. Notably, an enzyme conformation exiting the remodeling cycle reveals a linker DNA–sensing brake mechanism. Together, our findings elucidate a multistate model of ISWI action, providing a comprehensive mechanism of DNA translocation and regulation underpinning chromatin remodeling.
DOI: adu5654
Source: https://www.science.org/doi/10.1126/science.adu5654