Structure and regulation of the human INO80-nucleosome complex.
Structure and regulation of the human INO80-nucleosome complex.
复制标题
DOI：
10.1038/s41586-018-0021-6
复制
发表时间：
2018-04
期刊：
影响因子：
64.8
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Ayala R;Willhoft O;Aramayo RJ;Wilkinson M;McCormack EA;Ocloo L;Wigley DB;Zhang X
在细胞中的各种过程，包括转录、复制和修复，都需要进入核小体内的DNA。因此，细胞编码多个系统，重塑核小体。这些复合物可以是简单的，涉及一个或几个蛋白质亚基，或更复杂的多亚基机器。生化研究已经将几个重塑者的运动域置于核小体的超螺旋位置（SHL）2区域。Chd 1和Snf 2（RSC）与核小体复合物的结构研究为深入了解核小体通过这些复合物滑动的基本机制提供了新的思路。然而，更大的，多亚基重塑复合物，如INO 80，如何与核小体相互作用或重塑如何进行功能，如核小体滑动，组蛋白交换，核小体间距仍然知之甚少。虽然一些重塑剂作为单体起作用，但其他重塑剂作为高度协同的二聚体起作用。在这里，我们提出了INO 80染色质重塑与绑定核小体的结构，揭示了INO 80与核小体以独特的方式相互作用，其马达结构域位于组蛋白核心周围的包裹的入口点，而不是在SHL 2。INO 80的Arp 5-Ies 6模块在核小体的相对侧上形成额外的接触。这种独特的排列使得核小体的H3尾在调节中发挥作用，不同于其他特征性的重塑物。
Access to DNA within nucleosomes is required for a variety of processes in cells including transcription, replication and repair. Consequently, cells encode multiple systems that remodel nucleosomes. These complexes can be simple, involving one or a few protein subunits, or more complicated multi-subunit machines. Biochemical studies have placed the motor domains of several remodellers on the superhelical location (SHL) 2 region of the nucleosome. Structural studies on Chd1 and Snf2 (RSC) in complex with nucleosomes have provided insights into the basic mechanism of nucleosome sliding by these complexes. However, how larger, multi-subunit remodelling complexes, such as INO80, interact with nucleosomes or how remodellers carry out functions such as nucleosome sliding, histone exchange, and nucleosome spacing remains poorly understood. Although some remodellers work as monomers, others work as highly cooperative dimers. Here we present the structure of the INO80 chromatin remodeller with a bound nucleosome revealing that INO80 interacts with nucleosomes in a unique manner with the motor domains located at the entry point to the wrap around the histone core rather than at SHL2. The Arp5-Ies6 module of INO80 makes additional contacts on the opposite side of the nucleosome. This unique arrangement allows the H3 tails of the nucleosome to play a role in regulation, differing from other characterised remodellers.
登录
查看更多内容
电子计数和束诱导运动校正可实现近原子分辨率的单粒子冷冻电镜。
影响因子：
48
作者：
Li, Xueming;Mooney, Paul;Zheng, Shawn;Booth, Christopher R.;Braunfeld, Michael B.;Gubbens, Sander;Agard, David A.;Cheng, Yifan
通讯作者：
Cheng, Yifan
影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
影响因子：
5.6
作者：
Lowary, PT;Widom, J
通讯作者：
Widom, J
影响因子：
48
作者：
Punjani, Ali;Rubinstein, John L.;Brubaker, Marcus A.
通讯作者：
Brubaker, Marcus A.
影响因子：
14.9
作者：
Gerhold CB;Winkler DD;Lakomek K;Seifert FU;Fenn S;Kessler B;Witte G;Luger K;Hopfner KP
通讯作者：
Hopfner KP