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首页> 外文期刊>Biochemistry >Comprehensive DNA recognition through concerted interactions from adjacent zinc fingers
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Comprehensive DNA recognition through concerted interactions from adjacent zinc fingers

机译：通过相邻锌指之间的协调相互作用进行全面的DNA识别

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Zinc fingers are small DNA-binding modules noted for their occurrence in a large number of eukaryotic transcription factors, and their use in protein engineering. Although it was expected that zinc fingers can bind to a wide diversity of DNA sequences, previous studies using model zinc finger domains from Zif268 (and Sp1) have revealed a potential Limitation to the DNA-binding specificity. For example, phage display selection of individual zinc fingers to recognize trinucleotide DNA subsites returned fingers that bound specifically only to triplets of the form GNN, i.e., triplets with guanine at the 5' end. Following our recently reported work [Isalan, M., Choo, Y., and Klug, A. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 5617-5621], we now show that this limitation can be overcome by the concerted randomization of certain amino acid positions in adjacent zinc fingers that specify overlapping DNA subsites. This illustrates an important mechanism underlying DNA recognition by arrays of zinc fingers, and points the way to improved strategies for the design of highly specific zinc finger proteins that bind any given nucleotide sequence. [References: 24]
机译：锌指是小的DNA结合模块，因其在大量的真核转录因子中的存在及其在蛋白质工程中的用途而闻名。尽管人们期望锌指可以与各种各样的DNA序列结合，但是以前使用Zif268（和Sp1）的锌指模型域的研究显示了对DNA结合特异性的潜在限制。例如，噬菌体展示选择单个锌指以识别三核苷酸DNA亚位点，使返回的指仅特异性结合GNN形式的三联体，即在5'端带有鸟嘌呤的三联体。继我们最近报道的工作[Isalan，M.，Choo，Y.和Klug，A.（1997）Proc。 Natl。学院科学[U.S.A. 94，5617-5621]，我们现在表明，可以通过协调指定相邻DNA子位点的相邻锌指中某些氨基酸位置的一致随机化来克服这一局限。这说明了锌指阵列识别DNA的重要机制，并为改进设计策略的方法指明了途径，该策略设计了结合任何给定核苷酸序列的高特异性锌指蛋白。 [参考：24]

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