PDF(Pubmed)
Abstract：
The INO80 chromatin remodeler is a versatile enzyme capable of several functions, including spacing nucleosomes equal distances apart, precise positioning of nucleosomes based on DNA shape/sequence and exchanging histone dimers. Within INO80, the Arp5 subunit plays a central role in INO80 remodeling, evidenced by its interactions with the histone octamer, nucleosomal and extranucleosomal DNA, and its necessity in linking INO80\'s ATPase activity to nucleosome movement. Our investigation reveals that the grappler domain of Arp5 interacts with the acidic pocket of nucleosomes through two distinct mechanisms: an arginine anchor or a hydrophobic/acidic patch. These two modes of binding serve distinct functions within INO80 as shown in vivo by mutations in these regions resulting in varying phenotypes and in vitro by diverse effects on nucleosome mobilization. Our findings suggest that the hydrophobic/acidic patch of Arp5 is likely important for dimer exchange by INO80, while the arginine anchor is crucial for mobilizing nucleosomes.
摘要：
INO80染色质重塑剂是一种具有多种功能的多功能酶，包括将核小体间隔相等的距离，基于DNA形状/序列和交换组蛋白二聚体的核小体的精确定位。在INO80中，Arp5亚基在INO80重塑中起着核心作用，它与组蛋白八聚体的相互作用证明了这一点，核小体和核小体外DNA，以及将INO80的ATP酶活性与核小体运动联系起来的必要性。我们的研究表明，Arp5的抓斗结构域通过两种不同的机制与核小体的酸性口袋相互作用：精氨酸锚或疏水/酸性斑块。这两种结合模式在INO80中发挥不同的功能，如在体内通过这些区域中的突变导致不同的表型以及在体外通过对核小体动员的不同影响所示。我们的发现表明，Arp5的疏水/酸性斑块对于INO80的二聚体交换可能很重要，而精氨酸锚对于动员核小体至关重要。
