Selection of Protein-Protein Interactions of Desired Affinities with a Bandpass Circuit

利用带通电路选择具有所需亲和力的蛋白质-蛋白质相互作用

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Abstract

We have developed a genetic circuit in Escherichia coli that can be used to select for protein-protein interactions of different strengths by changing antibiotic concentrations in the media. The genetic circuit links protein-protein interaction strength to β-lactamase activity while simultaneously imposing tuneable positive and negative selection pressure for β-lactamase activity. Cells only survive if they express interacting proteins with affinities that fall within set high- and low-pass thresholds; i.e. the circuit therefore acts as a bandpass filter for protein-protein interactions. We show that the circuit can be used to recover protein-protein interactions of desired affinity from a mixed population with a range of affinities. The circuit can also be used to select for inhibitors of protein-protein interactions of defined strength.

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