Figure 10.
Schematic of control by phosphorylation. In the unphosphorylated state an auto-inhibitory (AI) segment of Apc1WD40 mimics the Cdc20 C-box motif and binds to the C-box binding site, blocking Cdc20 association. Initial Cdk-dependent phosphorylation of a kinase recruitment loop in Apc3 recruits Cdk-cyclin-Cks to the APC/C to facilitate intramolecular phosphorylation of the AI segment (when transiently displaced from the C-box binding site). The phosphorylated AI segment is stably displaced from the C-box binding site, permitting Cdc20 association to generate APC/CCdc20. This scheme indicates the relay mechanism by which initial phosphorylation of exposed consensus Cdk1 sites on Apc3 allow recruitment of Cks-Cdk-cyclin to the APC/C to promote intramolecular phosphorylation of Apc1. From Zhang et al. [60].