Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail
Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail
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DOI：
10.7554/elife.21477
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发表时间：
2017-01-21
期刊：
影响因子：
7.7
通讯作者：
Mueller-Planitz, Felix
中科院分区：
文献类型：
--
作者：
Ludwigsen, Johanna;Pfennig, Sabrina;Mueller-Planitz, Felix
ISWI家族的核小体重塑酶需要组蛋白H4的N端尾巴来动员核小体。在这里，我们映射了ISWI的H4-尾结合口袋。令人惊讶的是，结合位点在ISWI的N-末端区域(NTR)上与自动调节基序Auton相邻但不重叠，表明Auton并不像先前所认为的那样起简单的假底物的作用。相反，Auton与一个迄今尚未鉴定的基序AcidicN合作，赋予H4尾巴敏感性，并区分DNA和核小体。NTR中的第三个基序ppHSA在体内是功能所需的，并通过将NTR夹在ATPase结构域的叶2上提供结构稳定性。此配置让人想起Chd1，即使Chd1包含无关的NTR。我们的结果揭示了NTR对ISWI复杂的结构和功能调节，并发现了与Chd1惊人的相似之处
ISWI-family nucleosome remodeling enzymes need the histone H4 N-terminal tail to mobilize nucleosomes. Here we mapped the H4-tail binding pocket of ISWI. Surprisingly the binding site was adjacent to but not overlapping with the docking site of an auto-regulatory motif, AutoN, in the N-terminal region (NTR) of ISWI, indicating that AutoN does not act as a simple pseudosubstrate as suggested previously. Rather, AutoN cooperated with a hitherto uncharacterized motif, termed AcidicN, to confer H4-tail sensitivity and discriminate between DNA and nucleosomes. A third motif in the NTR, ppHSA, was functionally required in vivo and provided structural stability by clamping the NTR to Lobe 2 of the ATPase domain. This configuration is reminiscent of Chd1 even though Chd1 contains an unrelated NTR. Our results shed light on the intricate structural and functional regulation of ISWI by the NTR and uncover surprising parallels with Chd1