Two arginine residues suppress the flexibility of nucleosomal DNA in the canonical nucleosome core.
Two arginine residues suppress the flexibility of nucleosomal DNA in the canonical nucleosome core.
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DOI：
10.1371/journal.pone.0120635
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kurumizaka H
中科院分区：
文献类型：
--
作者：
Kono H;Shirayama K;Arimura Y;Tachiwana H;Kurumizaka H
使用分子动力学模拟研究了含有典型H3或其着丝粒特异性变体CENP-A的核小体的动力学。模拟结果表明，在100 ns和50 ns的模拟时间内，组蛋白核心的结构是稳定的，而DNA在入口和出口区域是高度灵活的，并从组蛋白核心部分解离。特别地，CENP-A核小体的入口和出口区域处的大约20-25 bp的DNA表现出比H3核小体的入口和出口区域处的DNA更大的波动。我们的详细分析阐明，这种动力学差异可归因于αN螺旋中两个碱性氨基酸的差异; H3中的两个精氨酸（Arg）残基被CENP-A中相应位点的赖氨酸（Lys）残基取代。这两个残基与DNA形成氢键能力的差异调节了核小体DNA在入口和出口区域的灵活性。我们的核酸外切酶III测定一致地显示，在H3核小体中这两个Arg残基被Lys替换增强了核酸内切酶的敏感性，这表明CENP-A核小体的DNA末端比H3核小体的DNA末端更灵活。这两种类型的核小体之间的动力学差异可能是重要的，在不同的阶段形成更高级的结构。
The dynamics of nucleosomes containing either canonical H3 or its centromere-specific variant CENP-A were investigated using molecular dynamics simulations. The simulations showed that the histone cores were structurally stable during simulation periods of 100 ns and 50 ns, while DNA was highly flexible at the entry and exit regions and partially dissociated from the histone core. In particular, approximately 20–25 bp of DNA at the entry and exit regions of the CENP-A nucleosome exhibited larger fluctuations than DNA at the entry and exit regions of the H3 nucleosome. Our detailed analysis clarified that this difference in dynamics was attributable to a difference in two basic amino acids in the αN helix; two arginine (Arg) residues in H3 were substituted by lysine (Lys) residues at the corresponding sites in CENP-A. The difference in the ability to form hydrogen bonds with DNA of these two residues regulated the flexibility of nucleosomal DNA at the entry and exit regions. Our exonuclease III assay consistently revealed that replacement of these two Arg residues in the H3 nucleosome by Lys enhanced endonuclease susceptibility, suggesting that the DNA ends of the CENP-A nucleosome are more flexible than those of the H3 nucleosome. This difference in the dynamics between the two types of nucleosomes may be important for forming higher order structures in different phases.
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作者：
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DOI：
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发表时间：
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