Overlaid positive and negative feedback loops shape dynamical properties of PhoPQ two-component system
Fig 2
PhoP-P is robust to overexpression of PhoP, PhoQ.
A—Modified PhoPQ TCS interaction network shows PhoQ binding MgrB, repressing PhoQ autophosphorylation (red arrow marks suppressed rate compared to unbound PhoQ autophosphorylation). This forms the interaction module. The interaction module takes 3 inputs (i) Stimulus (autophosphorylation rate), (ii) Total PhoP (PhoQ is assumed proportional, and 1/40 times PhoP based on actual measurements) and (iii) Total MgrB. Total protein is represented by subscript T in all figures and text. The system is numerically solved for a steady state concentration of PhoP-P as a function of varying PhoP, PhoQ total. The interaction module is coupled with a transcription module representing negative feedback with PhoP-P as input and total MgrB concentration as output. B—The system is solved numerically for steady state concentration of PhoP-P as a function of varying PhoP (and PhoQ) total (blue). PhoP-P is robust to PhoP/PhoQ concentrations, increasing further when PhoQ concentration is large enough to overcome MgrB negative feedback. Over most of the range of PhoQ concentrations, MgrB ≈ MgrB-total indicating large stoichiometric excess MgrB (orange line). Robustness breaks when MgrB is no longer in large excess of PhoQ. Dashed line indicates PhoP concentration estimated from measurements of Ref. [25].