Abstract

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.

中文翻译：

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通过可编程的DNA链置换实现动态蛋白质组装

摘要

受到天然蛋白质开关感知和响应各种环境队列的非凡能力的启发，在此我们报告一种通过使用DNA链置换来动态组织具有高度多样且复杂的逻辑门结构的蛋白质来设计合成蛋白质开关的策略。我们表明，DNA链位移可用于动态控制两个荧光蛋白之间的空间接近性和相应的荧光共振能量转移。通过执行布尔逻辑运算，可以使用多输入，可逆和扩增体系结构来明确控制蛋白质的接近性。通过实现酶级联反应的动态控制，我们进一步证明了该技术的强大功能。最后，