Circuit architecture explains functional similarity of bacterial heat shock responses

TL;DR

This study compares heat shock response systems in gram-negative and gram-positive bacteria, showing that despite different regulatory mechanisms, they exhibit similar dynamics constrained by specific chaperone-TF binding affinities.

Contribution

The paper introduces a mathematical model demonstrating how different bacterial heat shock systems can produce similar responses despite distinct regulatory architectures.

Findings

Both systems show similar heat shock dynamics.

Chaperone-TF binding affinities constrain system sensitivity.

Different regulatory mechanisms impose distinct binding affinity constraints.

Abstract

Heat shock response is a stress response to temperature changes and a consecutive increase in amounts of unfolded proteins. To restore homeostasis, cells upregulate chaperones facilitating protein folding by means of transcription factors (TF). We here investigate two heat shock systems: one characteristic to gram negative bacteria, mediated by transcriptional activator sigma32 in E. coli, and another characteristic to gram positive bacteria, mediated by transcriptional repressor HrcA in L. lactis. We construct simple mathematical model of the two systems focusing on the negative feedbacks, where free chaperons suppress sigma32 activation in the former, while they activate HrcA repression in the latter. We demonstrate that both systems, in spite of the difference at the TF regulation level, are capable of showing very similar heat shock dynamics. We find that differences in regulation impose distinct constrains on chaperone-TF binding affinities: the binding constant of free sigma32 to chaperon DnaK, known to be in 100 nM range, set the lower limit of amount of free chaperon that the system can sense the change at the heat shock, while the binding affinity of HrcA to chaperon GroE set the upper limit and have to be rather large extending into the micromolar range.