Dynamic protein assembly by programmable DNA strand displacement
Dynamic protein assembly by programmable DNA strand displacement
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DOI：
10.1038/s41557-018-0016-9
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发表时间：
2018-04-01
期刊：
影响因子：
21.8
通讯作者：
Chen, Wilfred
中科院分区：
文献类型：
--
作者：
Chen, Rebecca P.;Blackstock, Daniel;Chen, Wilfred
受天然蛋白质开关感知和响应各种环境队列的显着能力的启发，在这里，我们报告了一种策略，通过使用DNA链置换来动态组织具有高度多样性和复杂逻辑门架构的蛋白质，从而设计合成蛋白质开关。我们表明，DNA链置换可以用来动态控制空间接近和相应的荧光共振能量转移之间的两个荧光蛋白。执行布尔逻辑运算使得能够使用多输入、可逆和扩增架构来显式控制蛋白质接近度。我们通过实现酶级联的动态控制，进一步证明了这种技术超越传感的能力。最后，我们建立了实用的方法作为一个合成的计算平台，驱动动态重建的分裂酶靶向前药激活的基础上感测癌症特异性的miRNA。
Inspired by the remarkable ability of natural protein switches to sense and respond to a wide range of environmental queues, here we report a strategy to engineer synthetic protein switches by using DNA strand displacement to dynamically organize proteins with highly diverse and complex logic gate architectures. We show that DNA strand displacement can be used to dynamically control the spatial proximity and the corresponding fluorescence resonance energy transfer between two fluorescent proteins. Performing Boolean logic operations enabled the explicit control of protein proximity using multi-input, reversible and amplification architectures. We further demonstrate the power of this technology beyond sensing by achieving dynamic control of an enzyme cascade. Finally, we establish the utility of the approach as a synthetic computing platform that drives the dynamic reconstitution of a split enzyme for targeted prodrug activation based on the sensing of cancer-specific miRNAs.