Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Department of Physics, California Institute of Technology, Pasadena, CA 91125, USA.
Cell Syst. 2018 Apr 25;6(4):456-469.e10. doi: 10.1016/j.cels.2018.02.004. Epub 2018 Mar 21.
Allosteric regulation is found across all domains of life, yet we still lack simple, predictive theories that directly link the experimentally tunable parameters of a system to its input-output response. To that end, we present a general theory of allosteric transcriptional regulation using the Monod-Wyman-Changeux model. We rigorously test this model using the ubiquitous simple repression motif in bacteria by first predicting the behavior of strains that span a large range of repressor copy numbers and DNA binding strengths and then constructing and measuring their response. Our model not only accurately captures the induction profiles of these strains, but also enables us to derive analytic expressions for key properties such as the dynamic range and [EC]. Finally, we derive an expression for the free energy of allosteric repressors that enables us to collapse our experimental data onto a single master curve that captures the diverse phenomenology of the induction profiles.
变构调节存在于所有生命领域，但我们仍然缺乏简单、可预测的理论，无法将系统的实验可调参数直接与其输入-输出响应联系起来。为此，我们使用 Monod-Wyman-Changeux 模型提出了一种变构转录调控的一般理论。我们通过首先预测跨越大量阻遏物拷贝数和 DNA 结合强度范围的菌株的行为，然后构建和测量它们的响应，严格地测试了该模型。我们的模型不仅准确地捕捉了这些菌株的诱导谱，还使我们能够推导出关键特性（如动态范围和 EC）的解析表达式。最后，我们推导出了变构阻遏物的自由能表达式，使我们能够将实验数据折叠到单个主曲线上，该曲线捕捉了诱导谱的各种现象。
