Atomistic Simulation of Stacked Nucleosome Core Particles: Tail Bridging, the H4 Tail, and Effect of Hydrophobic Forces.
Atomistic Simulation of Stacked Nucleosome Core Particles: Tail Bridging, the H4 Tail, and Effect of Hydrophobic Forces.
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DOI：
10.1021/acs.jpcb.5b11863
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
S. Saurabh;M. Glaser;Y. Lansac;P. Maiti
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文献类型：
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作者：
S. Saurabh;M. Glaser;Y. Lansac;P. Maiti
我们报告了两个堆叠核小体核心颗粒 (NCP) 的首次原子模拟，旨在从分子细节上了解它们如何相互作用、盐浓度的影响以及不同组蛋白尾部如何促进它们的相互作用，特别强调 H4 尾部，已知它对 NCP-NCP 相互作用具有最大的稳定作用。与晶体学研究的结果相反，我们没有观察到 H4 尾部和 H2A-H2B 酸性斑块之间特定的 K16 介导的相互作用，但发现即使没有这种相互作用，堆叠也是稳定的。我们在 H4 尾部（部分/完全）移除的情况下进行模拟，发现 H4 尾部的 LYS-16 和 LYS-20 之间的区域在介导 NCP 间相互作用方面特别重要。在移除 H3 尾部的情况下执行类似的尾部修剪模拟，我们比较了 H3 和 H4 尾部在维持堆叠方面的作用。我们讨论了模拟结果与NCP在体外表现出的双层和其他液晶相的相关性，并通过组蛋白-组蛋白界面的分析，确定了可能稳定这些柱状中间相中NCP间相互作用的相互作用。通过使用引导分子动力学对堆叠核小体系统进行机械破坏，我们量化了在存在和不存在盐的情况下 NCP 间堆叠的强度。我们破坏了核小体间尾部-DNA 接触的一些特定位点的堆积，并对不同尾部在稳定堆积方面的结合强度进行了比较定量。我们还研究了疏水相互作用如何促进堆叠的整体稳定性，并发现疏水力与静电力在确定堆叠核小体系统稳定性方面的作用存在显着差异。
We report the first atomistic simulation of two stacked nucleosome core particles (NCPs), with an aim to understand, in molecular detail, how they interact, the effect of salt concentration, and how different histone tails contribute to their interaction, with a special emphasis on the H4 tail, known to have the largest stabilizing effect on the NCP-NCP interaction. We do not observe specific K16-mediated interaction between the H4 tail and the H2A-H2B acidic patch, in contrast with the findings from crystallographic studies, but find that the stacking was stable even in the absence of this interaction. We perform simulations with the H4 tail (partially/completely) removed and find that the region between LYS-16 and LYS-20 of the H4 tail holds special importance in mediating the inter-NCP interaction. Performing similar tail-clipped simulations with the H3 tail removed, we compare the roles of the H3 and H4 tails in maintaining the stacking. We discuss the relevance of our simulation results to the bilayer and other liquid-crystalline phases exhibited by NCPs in vitro and, through an analysis of the histone-histone interface, identify the interactions that could possibly stabilize the inter-NCP interaction in these columnar mesophases. Through the mechanical disruption of the stacked nucleosome system using steered molecular dynamics, we quantify the strength of inter-NCP stacking in the presence and absence of salt. We disrupt the stacking at some specific sites of internucleosomal tail-DNA contact and perform a comparative quantification of the binding strengths of various tails in stabilizing the stacking. We also examine how hydrophobic interactions may contribute to the overall stability of the stacking and find a marked difference in the role of hydrophobic forces as compared with electrostatic forces in determining the stability of the stacked nucleosome system.