Selection of zinc fingers that bind single-stranded telomeric DNA in the G-quadruplex conformation
Selection of zinc fingers that bind single-stranded telomeric DNA in the G-quadruplex conformation
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DOI：
10.1021/bi001728v
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发表时间：
2001-01-23
期刊：
影响因子：
2.9
通讯作者：
Choo, Y
中科院分区：
文献类型：
--
作者：
Isalan, M;Patel, SD;Choo, Y
有相当大的兴趣分子结合端粒DNA序列和g -四联体特异性。这些分子将有助于测试端粒长度调节的假设，并可能具有治疗潜力。锌指基序的多功能性和模块化特性使其成为工程g -四plex结合蛋白的理想候选者。噬菌体展示技术已广泛用于筛选锌指文库，以结合新的双链DNA序列。在这项研究中，已经筛选了一个三指文库，用于与含有以g -四重构象折叠的人类端粒重复序列的寡核苷酸结合的克隆。所选择的克隆显示出很强的氨基酸一致性，表明类似的结合模式。发现结合既依赖于序列又具有结构特异性。这是第一个工程蛋白与g -四重体DNA结合的例子，代表了锌指蛋白的一种新型结合相互作用。
There is considerable interest in molecules that bind to telomeric DNA sequences and G-quadruplexes with specificity. Such molecules would be useful to test hypotheses for telomere length regulation, and may have therapeutic potential. The versatility and modular nature of the zinc finger motif makes it an ideal candidate for engineering G-quadruplex-binding proteins. Phage display technology has previously been widely used to screen libraries of zinc fingers for binding to novel duplex DNA sequences. In this study, a three-finger library has been screened for clones that bind to an oligonucleotide containing the human telomeric repeat sequence folded in the G-quadruplex conformation. The selected clones show a strong amino acid consensus, suggesting analogous modes of binding. Binding was found to be both sequence dependent and structure specific. This is the first example of an engineered protein that binds to G-quadruplex DNA, and represents a new type of binding interaction for a zinc finger protein.