Temporal hierarchy of substrate degradation.

A, B, C: Transient response upon substrate addition. At t = 0 two substrates, S1 and S2 (each 300nM), are added to a steady state mixture containing Cul1, Cand1 and SR1-SR3. The resulting decline of the total amount of substrates is displayed together with the t_1/2 (dotted lines). Substrates with a higher SR affinity (A), substrates for SRs with a higher affinity for Cul1 (B) and substrates for more abundant SRs (C) are preferentially degraded.D, E, F: Assembly and disassembly of SCF ligases upon substrate addition. Depicted are changes in the fraction of SRs that are bound in a SCF complex. The blue and violet curves correspond to ([Cul1.SR1] + [Cul1.SR1.S1])/SR1_T and ([Cul1.SR2] + [Cul1.SR2.S2])/SR2_T, respectively, whereas the light red curve denotes [Cul1.SR3]/SR3_T. In each case Cul1 is redistributed from Cul1.SR3 into Cul1.SR1(.S1) and Cul1.SR2(.S2). In (A-F) if not indicated otherwise reference parameters are: K_S1 = K_S2 = 10nM (k_off = 1s⁻¹), K_sr,1 = K_sr,2 = K_sr,3 = 0.225pM, SR1_T = SR2_T = 60nM. To preserve detailed balance has been increased by a factor of 5 in (B) and (E). SR3_T = 660nM − (SR1_T + SR2_T), Cand1_T = 400nM, k_deg = 0.004s⁻¹. Parameters other than those mentioned are listed in Table 1.