Structural insights into chromatin remodeling by ISWI during active ATP hydrolysis

• 成果类型: Article
• 署名作者: Sia, Youyang; Pan, Han; Chen, Kangjing; Chen, Zhucheng
• 署名单位: Tsinghua University; Tsinghua University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11131
• DOI: 10.1126/science.adu5654
• 发表日期: 2025-06-05
• 关键词: nucleosome recognition; dna; mechanisms; mutations; swi2/snf2; FAMILY; domain

摘要

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.