The coactivators. (A) Structural organization of prototypical coactivators. The N-terminal domain is predicted to be largely unstructured. It contains the C box motif, whose sequence is displayed, and the KILR motif. Both motifs are believed to contribute to APC/C binding and activation. The KILR motif partly overlaps with a larger Mad2-interacting motif (MIM), which consists of ∼10 residues. The N-terminal region is followed by a seven-bladed β-propeller consisting of WD40 repeats. The short C-terminal extension terminates with the Ile-Arg (IR) motif, which also contributes to APC/C binding. N, N terminus; C, C terminus. (B) Cartoon model of the β-propeller of human Cdc20 bound to a KEN box motif shown in “sticks” mode (PDB ID: 4GGD; Tian et al., 2012). The triangle points to a region on the side of the toroid, distinct from the KEN binding site, where a putative D box binding site is positioned. (C) Molecular surface of the Cdc20-KEN motif from the same perspective as in B. The position of the three residues composing the KEN motif is indicated. (D) Cartoon model of Cdc20 from S. pombe bound to a BubR1 peptide mimicking a D box (Chao et al., 2012). To create this image, the atomic coordinates of the MCC complex (PDB ID: 4AEZ) were manipulated to remove Mad2 and Mad3/BubR1. The position of the KEN box of Mad3/BubR1 on the Cdc20 propeller is also shown. (E) Molecular surface of the Cdc20–D box mimic complex shown from the same perspective as in D. The consensus sequence of the D box is shown. (F) Negative stain EM reconstruction of APC/C^Cdh1 from S. cerevisiae (da Fonseca et al., 2011) with densities assigned to Cdh1 and Apc10. (G) Cryo–negative stain EM reconstruction of human APC/C^Cdh1 (Buschhorn et al., 2011). Densities assigned to Cdh1 and Apc10 are indicated.