Crystal structures of histone Sin mutant nucleosomes reveal altered protein-DNA interactions
Crystal structures of histone Sin mutant nucleosomes reveal altered protein-DNA interactions
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DOI：
10.1038/sj.emboj.7600046
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发表时间：
2004-01-28
期刊：
影响因子：
11.4
通讯作者：
Luger, K
中科院分区：
文献类型：
--
作者：
Muthurajan, UM;Bao, YH;Luger, K
在这里，我们描述了11个晶体结构的核小体核心颗粒含有个别点突变的结构区域的组蛋白H3和H4。突变的残基位于核小体二分体两侧的两个蛋白质- DNA界面处。其中5个突变部分恢复了酵母中SWI/SNF失活的体内效应。我们发现，即使这些残基的非保守突变（表现出不同的表型在体内）只有适度的影响，全球核小体结构。相反，局部蛋白质- DNA相互作用以微妙和复杂的方式被破坏和削弱。丢失的蛋白质- DNA相互作用的数量与组蛋白八聚体相对于DNA重新定位的倾向增加以及核小体的总体不稳定直接相关。因此，在核小体中，只有2 - 6个类似于120个组蛋白- DNA直接相互作用的破坏对核小体的移动性和稳定性有明显的影响。这对我们理解这些结构如何进入体内的转录和复制机制有影响。
Here we describe 11 crystal structures of nucleosome core particles containing individual point mutations in the structured regions of histones H3 and H4. The mutated residues are located at the two protein - DNA interfaces flanking the nucleosomal dyad. Five of the mutations partially restore the in vivo effects of SWI/SNF inactivation in yeast. We find that even nonconservative mutations of these residues ( which exhibit a distinct phenotype in vivo) have only moderate effects on global nucleosome structure. Rather, local protein - DNA interactions are disrupted and weakened in a subtle and complex manner. The number of lost protein - DNA interactions correlates directly with an increased propensity of the histone octamer to reposition with respect to the DNA, and with an overall destabilization of the nucleosome. Thus, the disruption of only two to six of the similar to120 direct histone - DNA interactions within the nucleosome has a pronounced effect on nucleosome mobility and stability. This has implications for our understanding of how these structures are made accessible to the transcription and replication machinery in vivo.