Overcoming the Cost of Positive Autoregulation by Accelerating the Response with a Coupled Negative Feedback.

ABSTRACT: A fundamental trade-off between rapid response and optimal expression of genes below cytotoxic levels exists for many signaling circuits, particularly for positively autoregulated systems with an inherent response delay. Here, we describe a regulatory scheme in the E. coli PhoB-PhoR two-component system, which overcomes the cost of positive feedback and achieves both fast and optimal steady-state response for maximal fitness across different environments. Quantitation of the cellular activities enables accurate modeling of the response dynamics to describe how requirements for optimal protein concentrations place limits on response speed. An observed fast response that exceeds the limit led to the prediction and discovery of a coupled negative autoregulation, which allows fast gene express

SUBMITTER: Gao R 

PROVIDER: S-EPMC6194859 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature