Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes

The yeast Chd1 protein acts to position nucleosomes across genomes. Here, we model the structure of the Chd1 protein in solution and when bound to nucleosomes. In the apo state, the DNA-binding domain contacts the edge of the nucleosome while in the presence of the non-hydrolyzable ATP analog, ADP-beryllium fluoride, we observe additional interactions between the ATPase domain and the adjacent DNA gyre 1.5 helical turns from the dyad axis of symmetry. Binding in this conformation involves unravelling the outer turn of nucleosomal DNA and requires substantial reorientation of the DNA-binding domain with respect to the ATPase domains. The orientation of the DNA-binding domain is mediated by sequences in the N-terminus and mutations to this part of the protein have positive and negative effects on Chd1 activity. These observations indicate that the unfavorable alignment of C-terminal DNA-binding region in solution contributes to an auto-inhibited state.

酵母Chd1蛋白的功能是在全基因组范围内排布核小体。本研究构建了Chd1蛋白在溶液中以及结合核小体时的结构模型。在空载（apo）状态下，其DNA结合结构域（DNA-binding domain）会接触核小体的边缘；而当加入非水解性ATP类似物ADP-铍氟化物时，我们观察到ATP酶结构域（ATPase domain）与距核小体对称双轴1.5个螺旋圈的邻近DNA袢产生了额外相互作用。该构象下的结合过程需要解开核小体DNA的外侧螺旋圈，同时要求DNA结合结构域相对于ATP酶结构域发生显著重定向。DNA结合结构域的定向由蛋白N端序列介导，对该区域进行的突变可对Chd1的活性产生双向影响。上述结果表明，溶液中C端DNA结合区域的不利取向是导致蛋白处于自抑制状态的重要原因。