Figure 7.

Schematic of ubiquitination reaction catalysed by the APC/C. (a) In the apo state, the downward position of the catalytic module would cause a clash between Apc5 and both UbcH10 and Apc2^WHB (as in the APC/C^{Cdh1.substrate}–UbcH10 ∼ ubiquitin complex). (b) Binding of coactivator shifts the catalytic module (Apc2 and Apc11) to an upward position. Apc2^CTD together with Apc2^WHB and Apc11^RING are highly flexible. Target lysines on the APC/C substrate are shown as ‘K’. (c) UbcH10-catalysed monoubiquitination. dU: UbcH10-conjugated donor ubiquitin. Apc2^WHB rigidifies by binding to UbcH10, Apc11^RING is less flexible. (d) UbcH10-catalysed multiubiquitination. The substrate-conjugated ubiquitin (U) engages the ubiquitin-binding exosite of Apc11^RING. (e) Ube2S-catalysed polyubiquitination. The distal acceptor ubiquitin (aU) of the polyubiquitin chain engages the ubiquitin-binding exosite of Apc11^RING positioning Lys 11 adjacent to the catalytic site of Ube2S. dU: donor ubiquitin conjugated to Ube2S. Dashed lines around Apc11^RING and Apc2^WHB denote conformational flexibility. Based on schemes from Brown et al. [112] and Chang & Barford [162].