APC/C ubiquitination reaction. (a) Apo APC/C. In the absence of coactivator the catalytic module adopts a ‘down’ inactive conformation. UbcH10 binding to Apc11RING is blocked by Apc5, and Apc5 prevents the correct location of Apc2WHB required to engage UbcH10. EM density for Apc11RING is weak indicating RING domain flexibility. PDB 5G05 from Zhang et al. [60]. (b) Complex of APC/CCdh1.substrate with a UbcH10 ∼ ubiquitin conjugate. Apc2WHB becomes ordered and engages UbcH10. dUb: modelled donor ubiquitin conjugated to UbcH10. The C-terminus of dUb is indicated with a red sphere. PDB 5A31, from Chang et al. [80]. PDB for Apc2WHB 4YII Chang et al. [111]. (c) APC/CCdh1.substrate-Ube2S∼Ub complex. Ube2S is partially built. aUb: acceptor ubiquitin bound to the Apc11RING exosite. PDB 5L9T, from Brown et al. [112]. The figure is based on previous work [60,80,111,112].