Engineering altered protein-DNA recognition specificity.
Engineering altered protein-DNA recognition specificity.
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DOI：
10.1093/nar/gky289
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发表时间：
2018-06-01
影响因子：
14.9
通讯作者：
Stoddard BL
中科院分区：
文献类型：
--
作者：
Bogdanove AJ;Bohm A;Miller JC;Morgan RD;Stoddard BL
蛋白质工程用于产生新的蛋白质折叠和组装，赋予现有蛋白质新的性质和功能，并增强我们对蛋白质结构原理的理解。虽然这些方法可以用于重编程蛋白质-蛋白质相互作用，但修饰蛋白质-DNA相互作用更加困难。这可能与蛋白质-DNA界面的结构特征有关，其显示出比可比蛋白质界面更多的带电基团、定向氢键、有序溶剂分子和抗衡离子。尽管如此，在重新设计蛋白质-DNA特异性方面已经取得了进展，其中大部分是由基因组修饰工程酶的开发所驱动的。在这里，我们总结了新的DNA特异性的锌指蛋白，大范围核酸酶，TAL效应，重组酶和限制性内切酶的创建。重新设计每个系统的容易性与蛋白质的模块性和蛋白质进化到能够响应自然选择而容易地改变其识别特异性的程度有关。显示出活性、特异性、可递送性和结果的理想组合的工程化DNA结合蛋白的开发不是完全解决的问题，然而，目前的每个平台都提供了独特的优势，被需要进一步研究和开发的行为和性质所抵消。
Protein engineering is used to generate novel protein folds and assemblages, to impart new properties and functions onto existing proteins, and to enhance our understanding of principles that govern protein structure. While such approaches can be employed to reprogram protein–protein interactions, modifying protein–DNA interactions is more difficult. This may be related to the structural features of protein–DNA interfaces, which display more charged groups, directional hydrogen bonds, ordered solvent molecules and counterions than comparable protein interfaces. Nevertheless, progress has been made in the redesign of protein–DNA specificity, much of it driven by the development of engineered enzymes for genome modification. Here, we summarize the creation of novel DNA specificities for zinc finger proteins, meganucleases, TAL effectors, recombinases and restriction endonucleases. The ease of re-engineering each system is related both to the modularity of the protein and the extent to which the proteins have evolved to be capable of readily modifying their recognition specificities in response to natural selection. The development of engineered DNA binding proteins that display an ideal combination of activity, specificity, deliverability, and outcomes is not a fully solved problem, however each of the current platforms offers unique advantages, offset by behaviors and properties requiring further study and development.
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影响因子：
3.7
作者：
Blount BA;Weenink T;Vasylechko S;Ellis T
通讯作者：
Ellis T
影响因子：
14.9
作者：
BOYD, AC;CHARLES, IG;BRAMMAR, WJ
通讯作者：
BRAMMAR, WJ
DOI：
10.1073/pnas.1533177100
发表时间：
2003-07-22
影响因子：
11.1
作者：
Akopian, A;He, JY;Stark, WM
通讯作者：
Stark, WM
影响因子：
56.9
作者：
Boch, Jens;Scholze, Heidi;Bonas, Ulla
通讯作者：
Bonas, Ulla
影响因子：
64.8
作者：
Ashworth, Justin;Havranek, James J.;Baker, David
通讯作者：
Baker, David