The histone H4 tail regulates the conformation of the ATP-binding pocket in the SNF2h chromatin remodeling enzyme.
The histone H4 tail regulates the conformation of the ATP-binding pocket in the SNF2h chromatin remodeling enzyme.
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DOI：
10.1016/j.jmb.2014.02.021
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发表时间：
2014-05-15
影响因子：
5.6
通讯作者：
Narlikar GJ
中科院分区：
文献类型：
--
作者：
Racki LR;Naber N;Pate E;Leonard JD;Cooke R;Narlikar GJ
染色质重塑复合物ACF有助于建立适当的核小体间距，以产生抑制的染色质状态。ACF活性由核小体底物的两个定义特征刺激：组蛋白H4 N-末端尾部上的基本补丁和侧翼DNA的特定长度。然而，这两种底物线索在ACF重塑反应中发挥作用的机制还不清楚。使用电子顺磁共振光谱与自旋标记的ATP类似物探测生理溶液条件下的ATP活性位点的结构，我们确定了一个封闭状态的ATP结合口袋，与ATP酶活性。我们发现，H4尾巴促进口袋关闭。我们进一步表明，ATP酶刺激的H4尾巴不需要一个特定的结构连接的H4尾巴和球状域。在许多DNA解旋酶的情况下，ATP结合口袋的闭合由特定的DNA底物调节。通过H4尾的口袋闭合可以类似地提供将底物识别与活性直接偶联的机制。令人惊讶的是，也刺激ATP水解的侧翼DNA并不促进口袋闭合，这表明H4尾和侧翼DNA可以在不同的反应步骤中被识别。
The chromatin remodeling complex ACF helps establish the appropriate nucleosome spacing for generating repressed chromatin states. ACF activity is stimulated by two defining features of the nucleosomal substrate: a basic patch on the histone H4 N-terminal tail and the specific length of flanking DNA. Yet the mechanisms by which these two substrate cues function in the ACF remodeling reaction is not well understood. Using electron paramagnetic resonance spectroscopy with spin-labeled ATP analogs to probe the structure of the ATP active site under physiological solution conditions, we identify a closed state of the ATP-binding pocket that correlates with ATPase activity. We find that the H4 tail promotes pocket closure. We further show that ATPase stimulation by the H4 tail does not require a specific structure connecting the H4 tail and the globular domain. In the case of many DNA helicases, closure of the ATP- binding pocket is regulated by specific DNA substrates. Pocket closure by the H4 tail may analogously provide a mechanism to directly couple substrate recognition to activity. Surprisingly, the flanking DNA, which also stimulates ATP hydrolysis, does not promote pocket closure, suggesting that the H4 tail and flanking DNA may be recognized in different reaction steps.
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