Structure of the primed state of the ATPase domain of chromatin remodeling factor ISWI bound to the nucleosome
Structure of the primed state of the ATPase domain of chromatin remodeling factor ISWI bound to the nucleosome
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DOI：
10.1093/nar/gkz670
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发表时间：
2019-09-26
影响因子：
14.9
通讯作者：
Subramaniam, Sriram
中科院分区：
文献类型：
--
作者：
Chittori, Sagar;Hong, Jingjun;Subramaniam, Sriram
SWI/SNF 2家族的ATP依赖性染色质重塑因子包括ISWI、SNF 2、CHD 1和INO 80亚家族，它们都具有一个保守的但功能上不可互换的ATP酶结构域。在这里，我们报告冷冻电子显微镜（cryo-EM）结构的核小体绑定到一个ISWI片段与删除的AutoN和HSS区域在无核苷酸的条件下和自由核小体在类似4埃分辨率。在结合构象中，ATP酶结构域与核小体DNA的超螺旋位置2（SHL 2）、H4的N-末端尾和H3的α 1螺旋相互作用。没有观察到ISWI其他区域的密度，可能是由于无序。与游离核小体的结构比较表明，虽然组蛋白核心基本保持不变，重塑剂结合导致核小体DNA中的扰动，导致SHL 2位点附近的凸起。总体而言，无核苷酸ISWI-核小体复合物的结构与最近报道的ADP结合ISWI-核小体结构的相应区域相似，这与ADP-BeFx结合结构观察到的显著不同。我们的研究结果与ISWI与核小体结合的初始步骤有关，并为ISWI驱动的核小体重塑过程提供了额外的见解。
ATP-dependent chromatin remodeling factors of SWI/SNF2 family including ISWI, SNF2, CHD1 and INO80 subfamilies share a conserved but functionally non-interchangeable ATPase domain. Here we report cryo-electron microscopy (cryo-EM) structures of the nucleosome bound to an ISWI fragment with deletion of the AutoN and HSS regions in nucleotide-free conditions and the free nucleosome at similar to 4 angstrom resolution. In the bound conformation, the ATPase domain interacts with the super helical location 2 (SHL 2) of the nucleosomal DNA, with the N-terminal tail of H4 and with the alpha 1 helix of H3. Density for other regions of ISWI is not observed, presumably due to disorder. Comparison with the structure of the free nucleosome reveals that although the histone core remains largely unchanged, remodeler binding causes perturbations in the nucleosomal DNA resulting in a bulge near the SHL2 site. Overall, the structure of the nucleotide-free ISWI-nucleosome complex is similar to the corresponding regions of the recently reported ADP bound ISWI-nucleosome structures, which are significantly different from that observed for the ADP-BeFx bound structure. Our findings are relevant to the initial step of ISWI binding to the nucleosome and provide additional insights into the nucleosome remodeling process driven by ISWI.