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首页> 外文期刊>Journal of Computer-Aided Molecular Design >The role of zinc finger linkers in zinc finger protein binding to DNA
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The role of zinc finger linkers in zinc finger protein binding to DNA

机译：锌指接头在锌指蛋白与DNA结合中的作用

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摘要

Zinc finger proteins (ZFP) play important roles in cellular processes. The DNA binding region of ZFP consists of 3 zinc finger DNA binding domains connected by amino acid linkers, the sequence TGQKP connects ZF1 and ZF2, and TGEKP connects ZF2 with ZF3. Linkers act to tune the zinc finger protein in the right position to bind its DNA target, the type of amino acid residues and length of linkers reflect on ZF1-ZF2-ZF3 interactions and contribute to the search and recognition process of ZF protein to its DNA target. Linker mutations and the affinity of the resulting mutants to specific and nonspecific DNA targets were studied by MD simulations and MM_GB(PB)SA. The affinity of mutants to DNA varied with type and position of amino acid residue. Mutation of K in TGQKP resulted in loss in affinity due to the loss of positive K interaction with phosphates, mutation of G showed loss in affinity to DNA, WT protein and all linker mutants showed loss in affinity to a nonspecific DNA target, this finding confirms previous reports which interpreted this loss in affinity as due to ZF1 having an anchoring role, and ZF3 playing an explorer role in the binding mechanism. The change in ZFP-DNA affinity with linker mutations is discussed in view of protein structure and role of linker residues in binding.
机译：锌指蛋白（ZFP）在细胞过程中起着重要作用。ZFP的DNA结合区由3个通过氨基酸接头连接的锌指DNA结合域组成，TGQKP序列连接ZF1和ZF2，TGEKP连接ZF2和ZF3。接头的作用是将锌指蛋白调整到正确的位置以结合其 DNA 靶标，氨基酸残基的类型和接头的长度反映了 ZF1-ZF2-ZF3 相互作用，并有助于 ZF 蛋白对其 DNA 靶标的搜索和识别过程。通过MD模拟和MM_GB（PB）SA研究了接头突变以及所得突变体对特异性和非特异性DNA靶标的亲和力。突变体对DNA的亲和力随氨基酸残基的类型和位置而变化。由于 K 与磷酸盐的正相互作用丧失，TGQKP 中 K 的突变导致亲和力丧失，G 突变显示对 DNA 的亲和力丧失，WT 蛋白和所有接头突变体都显示出对非特异性 DNA 靶标的亲和力丧失，这一发现证实了先前的报道，这些报道将这种亲和力的丧失解释为由于 ZF1 具有锚定作用， ZF3 在绑定机制中起着探索者的作用。结合蛋白质结构和接头残基在结合中的作用，讨论了ZFP-DNA亲和力与接头突变的变化。

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