Specificity of protein-DNA recognition revealed by structure-based potentials: Symmetric/asymmetric and cognate/non-cognate binding
Specificity of protein-DNA recognition revealed by structure-based potentials: Symmetric/asymmetric and cognate/non-cognate binding
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DOI：
10.1016/s0022-2836(02)00846-x
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发表时间：
2002-10-04
影响因子：
5.6
通讯作者：
Sarai, A
中科院分区：
文献类型：
--
作者：
Selvaraj, S;Kono, H;Sarai, A
在许多蛋白质-DNA复合物中观察到的蛋白质同源二聚体与DNA的不对称结合导致两个亚基之间的细微结构差异。当亚基分别形成同源和非同源蛋白质-DNA复合物时，经常观察到这种结构差异。这些结构上的结合特异性的影响分析，应提供深入了解蛋白质-DNA识别的机制。我们之前从许多蛋白质-DNA复合物结构的统计分析中推导出特定核苷酸碱基-氨基酸相互作用的经验势函数，并使用组合线程程序来评估所涉及的DNA序列的适合度。然后，我们引入了Z分数来测量蛋白质与复合物内的DNA结合的特异性，与随机DNA序列相比。在这里，我们详细研究了不对称和同源/非同源结合对特异性的结构影响。在X阻遏物的两个亚基（糖皮质激素受体）和含有Zn（2）Cys（6）双核簇结构域的转录因子（已知其与DNA不对称结合）中观察到DNA结合特异性的显著差异。此外，Bam H1和Eco RV核酸内切酶与其同源和非同源DNA序列结合的特异性的差异使用这种方法被清楚地检测到;事实上，EcoRV结合的分析使我们能够显示序列和结构对结合特异性的协同作用。目前的结果表明，这种方法的效用时，检查在蛋白质-DNA识别的结构特异性关系，在对称/不对称和同源/非同源结合的细微结构差异清楚地表明，导致显着的特异性差异。该方法也可用作检查蛋白质-DNA复合物的新结构的特异性的工具。(C)2002爱思唯尔科技有限公司。保留所有权利。
Asymmetric binding of protein homodimers to DNA, which has been observed in a number of protein-DNA complexes, leads to subtle structural differences between the two subunits. Such structural differences are frequently observed when the subunits form cognate and non-cognate protein-DNA complexes, respectively. Analysis of these structural effects on binding specificity should provide insight into the mechanism of protein-DNA recognition. We previously derived empirical potential functions for specific nucleotide base-amino acid interactions from statistical analyses of the structures of many protein-DNA complexes and used a combinatorial threading procedure to evaluate the fitness of the DNA sequences involved. We then introduced Z-scores to measure the specificity with which proteins bind to DNA within complexes, as compared to random DNA sequences. Here, we examined in detail the structural effects of asymmetric and cognate/non-cognate binding on specificity. Marked differences in the specificity of DNA binding were observed for the two subunits of X repressor, the glucocorticoid receptor, and for transcription factors containing a Zn(2)Cys(6) binuclear cluster domain, which are known to bind asymmetrically to DNA. Moreover, the differences in the specificity with which Bam H1 and Eco RV endonucleases bind to their cognate and non-cognate DNA sequences were clearly detected using this approach; indeed, analysis of EcoRV binding enabled us to show the cooperative effect of sequence and structure on binding specificity. The present results demonstrate the utility of this approach when examining the structure-specificity relationship in protein-DNA recognition, as subtle structural differences in symmetric/ asymmetric and cognate/non-cognate binding were clearly shown to cause marked differences in specificity. This method can also be used as a tool for checking new structures of protein-DNA complexes for their specificity. (C) 2002 Elsevier Science Ltd. All rights reserved.