Structural analysis of conserved base pairs in protein-DNA complexes
Structural analysis of conserved base pairs in protein-DNA complexes
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DOI：
10.1093/nar/30.7.1704
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发表时间：
2002-04-01
影响因子：
14.9
通讯作者：
Gelfand, MS
中科院分区：
文献类型：
--
作者：
Mirny, LA;Gelfand, MS
了解蛋白质-DNA 相互作用对于预测转录因子的 DNA 结合特异性和设计新型 DNA 结合蛋白至关重要。在本文中，我们开发了一种分析蛋白质-DNA 相互作用的新方法。我们汇集了两个信息来源：(i) 蛋白质-DNA 复合物的结构（PDB/NDB 数据库）和 (ii) 通过实验获得的 DNA 结合蛋白识别的位点。位点用于计算每个碱基对的保守性（信息内容），这表明碱基对在特定识别中的相对重要性。这项研究的主要结果是，一个位点中碱基对的保守性与碱基对与蛋白质的接触数量表现出显着的相关性。特别是，与蛋白质接触较多的碱基对在进化中更加保守。尽管很自然，但这个结果以前从未被报道过。我们还观察到，对于大多数研究的蛋白质，氢键和疏水相互作用本身无法解释结合位点的进化保守模式，这表明不同类型的相互作用对特定识别的累积贡献。讨论了 DNA 结合特异性预测的意义。
Understanding of protein-DNA interactions is crucial for prediction of DNA-binding specificity of transcription factors and design of novel DNA-binding proteins. In this paper we develop a novel approach to analysis of protein-DNA interactions. We bring together two sources of information: (i) structures of protein-DNA complexes (PDB/NDB database) and (ii) experimentally obtained sites recognized by DNA-binding proteins. Sites are used to compute conservation (information content) of each base pair, which indicates relative importance of the base pair in specific recognition. The main result of this study is that conservation of base pairs in a site exhibits significant correlation with the number of contacts the base pairs have with the protein. In particular, base pairs that have more contacts with the protein are more conserved in evolution. As natural as it is, this result has never been reported before. We also observe that for most of the studied proteins, hydrogen bonds and hydrophobic interactions alone cannot explain the pattern of evolutionary conservation in the binding site suggesting cumulative contribution of different types of interactions to specific recognition. Implications for prediction of the DNA-binding specificity are discussed.