Extended Data Figure 9: Model of the effects of apcin and TAME on formation of the APC/C–Cdc20–substrate ternary complex.

a, Schematic drawing of core APC/C subunits. Not all subunits are indicated, and not all known interactions between subunits are illustrated for the sake of simplicity. The light blue oval and polygon indicate binding sites for Cdc20 on core APC/C subunits. b, In the absence of substrate, Cdc20 (green) can bind to the APC/C via the C-box (labelled ‘C’), which interacts with APC8, and the IR-tail (labelled ‘IR’), which interacts with APC3 (Cdc27). c, Binding of substrates (red) that contain a D-box (labelled ‘D’) can promote formation of a co-receptor interaction between the WD-40 ___domain of Cdc20 and Apc10. d, The RING-containing subunit APC11 can recruit the E2 enzyme to conjugate ubiquitin to the substrate. e, TAME binds APC3 to interfere with the IR-tail binding site. f, Apcin binds to the leucine pocket of the WD-40 ___domain of Cdc20. g, In the presence of TAME (labelled ‘T’), the IR-binding site is disrupted, but Cdc20 can still be recruited to the APC/C through the C-box interaction and co-receptor interaction. h, Apcin (labelled ‘A’) can disrupt the D-box interaction between the substrate and Cdc20, but Cdc20 can still interact through the C-box and IR-tail interactions. i, Combined use of apcin and TAME disrupts both interactions, cooperatively disrupting the interaction between APC/C, Cdc20 and substrate.