Intermolecular and intramolecular readout mechanisms in protein-DNA recognition
Intermolecular and intramolecular readout mechanisms in protein-DNA recognition
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DOI：
10.1016/j.jmb.2004.01.033
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发表时间：
2004-03-19
影响因子：
5.6
通讯作者：
Sarai, A
中科院分区：
文献类型：
--
作者：
Gromiha, MM;Siebers, JG;Sarai, A
蛋白质-DNA 识别在基因表达的调控中发挥着重要作用。已知调节蛋白可通过原子接触（分子间读出）直接识别特定的 DNA 序列和/或通过 DNA 的构象特性（分子内读出）间接识别特定的 DNA 序列。然而，人们对这些所谓的直接和间接读出机制各自的贡献知之甚少。 We addressed this question by making use of information extracted from a structural database containing many protein-DNA complexes. 2 我们通过对蛋白质-DNA 复合物内的碱基-氨基酸相互作用进行统计分析，量化了分子间（直接）读数的特异性。通过对序列依赖性 DNA 构象的统计分析来量化 DNA 引起的分子内（间接）读数的特异性。对大量蛋白质-DNA 复合物中这些特异性的系统比较表明，分子间和分子内读数都有助于蛋白质-DNA 识别的特异性，并且它们的相对贡献根据蛋白质-DNA 复合物而变化。我们证明，统计分析得出的分子间和分子内能量的组合可以增强特异性，并且组合的能量可以解释由碱基突变引起的结合亲和力变化的实验数据。这些结果为蛋白质-DNA 识别过程中特异性和结构之间的关系提供了新的见解，从而可以预测特定的蛋白质-DNA 结合位点。 (C) 2004 Elsevier Ltd. 保留所有权利。
Protein-DNA recognition plays an essential role in the regulation of gene expression. Regulatory proteins are known to recognize specific DNA sequences directly through atomic contacts (intermolecular readout) and/or indirectly through the conformational properties of the DNA (intramolecular readout). However, little is known about the respective contributions made by these so-called direct and indirect readout Mechanisms. We addressed this question by making use of information extracted from a structural database containing many protein-DNA complexes. 2 We quantified the specificity of intermolecular (direct) readout by statistical analysis of base-amino acid interactions within protein-DNA complexes. The specificity of the intramolecular (indirect) readout due to DNA was quantified by statistical analysis of the sequence-dependent,, DNA conformation. Systematic comparison of these specificities in a large number of protein-DNA complexes revealed that both intermolecular and intramolecular readouts contribute to the specificity of protein-DNA recognition, and that their relative contributions vary depending upon the protein-DNA complexes. We demonstrated that combination of the intermolecular and intramolecular energies derived from the statistical analyses lead to enhanced specificity, and that the combined energy could explain experimental data on binding affinity changes caused by base mutations. These results provided new insight into the relationship between specificity and structure in the process of protein-DNA recognition, which would lead to prediction of specific protein-DNA binding sites. (C) 2004 Elsevier Ltd. All rights reserved.