首页> 外文期刊>Journal of Molecular Biology >Recognition of 5'-YpG-3' Sequences by Coupled Stacking/Hydrogen Bonding Interactions with Amino Acid Residues.
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Recognition of 5'-YpG-3' Sequences by Coupled Stacking/Hydrogen Bonding Interactions with Amino Acid Residues.

机译:通过与氨基酸残基偶联的堆积/氢键相互作用识别5'-YpG-3'序列。

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摘要

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.
机译:数百种蛋白质-DNA复合物的生物化学和结构研究相结合,表明特定于序列的相互作用是通过直接和间接读出的两种机制介导的。直接读出涉及蛋白质与DNA的主要和次要凹槽中暴露的碱基特异性原子之间的直接相互作用。对于间接读出,蛋白质通常通过与磷酸二酯主链相互作用,通过检测取决于核苷酸序列的结构构象变化来识别DNA。基于我们与DNA结合的Ndt80的最新结构,以及对现有PDB数据库的搜索,我们提出了一种利用直接和间接读出的序列特异性识别新方法。在这种模式下,单个氨基酸侧链可识别两个连续的碱基对。 3'碱基可通过规范直接读出来识别,而5'碱基可通过间接读出的变化来识别,从而特定二核苷酸步骤(即5'-嘧啶-嘌呤-3'步骤)的构象柔性,通过阳离子-pi相互作用促进氨基酸识别。在大多数情况下,这种DNA识别模式有助于解释蛋白质对其靶DNA的序列特异性。

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