Figure 3

Combination of avidity with a product-inhibition negative feedback loop provides robustness to the PEP formation rate. a) A schematic illustration of how the PPi negative feedback leads the output PEP formation rate back to its robust level upon a step addition of PPDK protein. (1) An increase in total PPDK levels leads to a rise in PPDK₀ levels. In turn, (2) PPDK₁ and PPi rise. (3) PPi rise leads to inhibition of the phosphatase activity of RP (product inhibition) and (4) to a rise in PPDK₂ levels, lowering PPDK₁ amounts. (5) The decrease in PPDK₁ yields a decrease in PPDK₀ and thus leads to (6) a decrease in PPi and rise of RP phosphatase rate. The robust formation rate, F*, is again attained. Since the avidity mechanism places both the kinase and phosphatase reactions from the same complex (ternary complex), steady-state requires only that their rates are equal (regardless of protein levels). Thus, steady state formation rate goes back to its original state, while the extra amount of PPDK is routed to the PPDK₂ state, which acts as a buffer. Grey circles indicate deviations from the initial steady-state and green (red) arrows indicate increased (decreased) levels. b) Schematic illustration of the system's dynamics upon an increase in PPDK total amounts. The numbers in the different plots mark the phases of the system's adaptation back to the robust solution as marked in a).