Fig. 7.

Mechanism of how cyclin A2 evades the SAC and conversion of cyclin B1 into a prometaphase substrate. a Schematic cartoon showing that Cdk-cyclinA2-Cks2 associates with APC/C^MCC and displaces the ABBA motif (A2) and the D box (D2) of BubR1 from Cdc20^M. The more exposed KEN-box binding site on Cdc20^A is likely to accommodate the KEN box of cyclin A2. Binding of cyclin A2 may induce the open state MCC. We propose that the D2 box is the principle D box; however, the D1 box augments affinity through an avidity effect. Bottom: Schematic of BubR1 domain organization showing its degrons and the respective interacting Cdc20 subunits. b Close-up view of a model with cyclin A2 associating with Cdc20^A-MCC (PDB 5LCW²²). Cyclin A2 degrons are shown modelled as surface representations in orange occupying the more exposed degron-binding sites based on the equivalent pseudo-degrons of BubR1²². The remaining three degron-binding sites where BubR1 degrons could still engage are highlighted as red spheres (A1, D1, K1). c, d Insertion of both the KEN box and ABBA motif into cyclin B1 allowed it to resist MCC-imposed inhibition (compare lanes 1, 2 and 9, 10). Cyclin B1 is in complex with Cdk2-Cks2. The histogram of relative APC/C^MCC activity is normalized to respective APC/C^Cdc20 activity, with error bars indicating standard deviation, and significance is calculated using unpaired Student’s t-test (indicated with stars, n = 2, Supplementary Table 2). Source data are provided as a Source Data file