Figure 4. Ultrasensitivity contributes to metabolic compensation.

1. The time series of the total input KaiC phosphorylation level (purple, left scale) and residual KaiA concentration not precipitated with KaiB‐FLAG (gray, right scale).
2. A schematic of the oscillator model by Phong et al (2013). Here, ^BC^S and ^BC^D represent the KaiB‐bound S and D phosphoforms, respectively, which can sequester KaiA. The dashed line represents the effect of introducing ultrasensitivity to the model.
3. A cartoon representation of introducing a KaiA sequestration affinity, K _D, into the Phong model. The original model has an effectively infinite sequestration affinity (dashed curve).
4. A cartoon representation of introducing a KaiA threshold to the Michaelis–Menten‐type phosphorylation rate constant in the Phong model.
5. The period of the oscillator model as a function of %ATP and K _D, a measure of KaiA sequestration affinity, without (top) or with (bottom) a phosphorylation threshold. All model simulations were done with 3.5 μM of KaiC and 1.5 μM of KaiA. White regions indicate unstable or no oscillation.
6. The extent to which KaiA can be sequestered by KaiB depends on the maximal S and D phosphoform concentration, $[{\mathrm{C}}_{\max }^{\mathrm{S}+\mathrm{D}}]$, achieved over the phosphorylation cycle. The scaling of the EC50 of the phosphorylation stimulus–response function, which is a measure of the capacity of the U phosphoform to suppress KaiA activity, compensates for the scaling of $[{\mathrm{C}}_{\max }^{\mathrm{S}+\mathrm{D}}]$ with %ATP.