Recognition of 5'-YpG-3' sequences by coupled stacking/hydrogen bonding interactions with amino acid residues
Recognition of 5'-YpG-3' sequences by coupled stacking/hydrogen bonding interactions with amino acid residues
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DOI：
10.1016/j.jmb.2003.10.071
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发表时间：
2004-01-09
影响因子：
5.6
通讯作者：
Glover, JNM
中科院分区：
文献类型：
--
作者：
Lamoureux, JS;Maynes, JT;Glover, JNM
对数百个蛋白质-DNA复合体的生化和结构的联合研究表明，序列特异性的相互作用由两种机制介导，称为直接读出和间接读出。直接读出涉及蛋白质与暴露在DNA主要和次要凹槽中的碱基特定原子之间的直接相互作用。对于间接读出，蛋白质通过感知依赖于核苷酸序列的结构的构象变化来识别DNA，通常是通过与磷酸二酯骨架的相互作用。基于我们最近与DNA结合的Ndt80的结构，结合对现有PDB数据库的搜索，我们提出了一种新的利用直接和间接读出的序列特异性识别方法。在这种模式下，单个氨基酸侧链识别两个连续的碱基对。3‘-碱基是通过正则直接读出识别的，而5’-碱基是通过间接读出的变体识别的，因此特定二核苷酸步骤的构象灵活性，即5‘-嘧啶-嘌呤-3’步骤，有助于氨基酸通过阳离子-pi相互作用识别它。在大多数情况下，这种DNA识别模式有助于解释蛋白质对其目标DNA的序列特异性。(C)2003爱思唯尔有限公司。保留所有权利。
The combined biochemical and structural study of hundreds of protein-DNA complexes has indicated that sequence-specific interactions are mediated by two mechanisms termed direct and indirect readout. Direct readout involves direct interactions between the protein and base-specific atoms exposed in the major and minor grooves of DNA. For indirect readout, the protein recognizes DNA by sensing conformational variations in the structure dependent on nucleotide sequence, typically through interactions with the phosphodiester backbone. Based on our recent structure of Ndt80 bound to DNA in conjunction with a search of the existing PDB database, we propose a new method of sequence-specific recognition that utilizes both direct and indirect readout. In this mode, a single amino acid side-chain recognizes two consecutive base-pairs. The 3'-base is recognized by canonical direct readout, while the 5'-base is recognized through a variation of indirect readout, whereby the conformational flexibility of the particular dinucleotide step, namely a 5'-pyrimidine-purine-3' step, facilitates its recognition by the amino acid via cation-pi interactions. In most cases, this mode of DNA recognition helps explain the sequence specificity of the protein for its target DNA. (C) 2003 Elsevier Ltd. All rights reserved.