Howard Hughes Medical Institute, Center for Computational Biology and Bioinformatics, Columbia University, New York, NY 10032, USA.
Annu Rev Biochem. 2010;79:233-69. doi: 10.1146/annurev-biochem-060408-091030.
Specific interactions between proteins and DNA are fundamental to many biological processes. In this review, we provide a revised view of protein-DNA interactions that emphasizes the importance of the three-dimensional structures of both macromolecules. We divide protein-DNA interactions into two categories: those when the protein recognizes the unique chemical signatures of the DNA bases (base readout) and those when the protein recognizes a sequence-dependent DNA shape (shape readout). We further divide base readout into those interactions that occur in the major groove from those that occur in the minor groove. Analogously, the readout of the DNA shape is subdivided into global shape recognition (for example, when the DNA helix exhibits an overall bend) and local shape recognition (for example, when a base pair step is kinked or a region of the minor groove is narrow). Based on the >1500 structures of protein-DNA complexes now available in the Protein Data Bank, we argue that individual DNA-binding proteins combine multiple readout mechanisms to achieve DNA-binding specificity. Specificity that distinguishes between families frequently involves base readout in the major groove, whereas shape readout is often exploited for higher resolution specificity, to distinguish between members within the same DNA-binding protein family.
蛋白质与 DNA 之间的特异性相互作用是许多生物过程的基础。在这篇综述中，我们提供了一个对蛋白质-DNA 相互作用的修正观点，强调了两种大分子三维结构的重要性。我们将蛋白质-DNA 相互作用分为两类：一类是当蛋白质识别 DNA 碱基的独特化学特征时（碱基读取），另一类是当蛋白质识别序列依赖性 DNA 形状时（形状读取）。我们进一步将碱基读取分为在大沟中发生的相互作用和在小沟中发生的相互作用。类似地，DNA 形状的读取也分为全局形状识别（例如，当 DNA 螺旋呈现整体弯曲时）和局部形状识别（例如，当碱基对步弯曲或小沟区域变窄时）。基于现在在蛋白质数据库中可用的>1500 个蛋白质-DNA 复合物结构，我们认为单个 DNA 结合蛋白结合多种读取机制来实现 DNA 结合特异性。区分家族的特异性通常涉及大沟中的碱基读取，而形状读取则经常用于更高分辨率的特异性，以区分同一 DNA 结合蛋白家族中的成员。
