Optimal Cand1 concentration.

A: Extension of the model depicted in Fig 1B. Substrate (S1) reversibly binds to Cul1.SR1. The substrate in the resulting Cul1.SR1.S1 complex is degraded with effective rate constant k_deg. B: Time courses showing the degradation of total substrate S_T = [S1] + [Cul1.SR1.S1]. At t = 0 substrate (300nM) was added to a steady state mixture containing SR1_T = 30nM, SR2_T = 630nM and Cand1_T as indicated. Note that t_1/2 changes non-monotonically as a function of Cand1_T. C: Half-life for substrate degradation (t_1/2) as a function of Cand1_T for decreasing binding affinity. As the association rate constant k_on for substrate binding decreases t_1/2 increases and the dependence of t_1/2 on Cand1_T becomes monotonic. Parameters for substrate binding: k_on = 10⁸M⁻¹s⁻¹, k_off = 1s⁻¹, k_deg = 0.004s⁻¹. Parameters other than those mentioned are listed in Table 1.