A speculative model of protein ubiquitination by the APC. Substrate (magenta) is likely to bind multivalently to both activator and the APC using degradation sequences (red rectangles) in disordered substrate regions. The APC positions substrates so that multiple lysine side chains can effectively attack the E2-ubiquitin bond. Residues near the E2 active site promote catalysis, which is stimulated upon binding to the APC. Flexibility in both the substrate and APC may help accommodate the modification of many lysines and the formation of long polyubiquitin chains.