2025-04-17 清華大学
(A) Heatmap of DNA phosphate backbone displacement. Relative to the ATP state, both DNA strands in ADP* shift inward (arrow direction), and a 1-bp DNA bulge is stored at SHL2
(B) Structural comparison of SHL2 DNA in ATP (gray) and ADP* (colored) states.
(C) Cryo-EM density map of the DNA bulge in the ADP* state.
(D) Analysis of local histone-DNA interactions. ATP state (gray); ADP* state (colored). In ADP*, histone-DNA interactions are disrupted.
<関連情報>
- https://www.tsinghua.edu.cn/en/info/1245/14192.htm
- https://www.science.org/doi/10.1126/science.adu5654
活性型ATP加水分解におけるISWIによるクロマチンリモデリングの構造的洞察 Structural insights into chromatin remodeling by ISWI during active ATP hydrolysis
Youyang Sia, Han Pan, Kangjing Chen, and Zhucheng Chen
Science Published:3 Apr 2025
DOI:https://doi.org/10.1126/science.adu5654
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 are distorted accordingly, showing one full base-pair bulge and a loss of histone contact at the site of motor binding in the adenosine diphosphate* b and Apo* states. We also identify 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.
