Anaphase-promoting Complex - APC/C Subunits

APC/C Subunits

The catalytic core of the APC/C consists of the cullin subunit Apc2 and RING H2 domain subunit Apc11. These two subunits catalyze ubiquitylation of substrates when the C-terminal domain of Apc2 forms a tight complex with Apc11. In addition to the catalytic subunits, other core proteins of the APC are composed multiple repeat motifs with the main purpose of providing molecular scaffold support. These include Apc1, the largest subunit which contains 11 tandem repeats of 35-40 amino acid sequences, and Apc2, which contains three cullin repeats of approximately 130 amino acids total.

Most notably, 4 subunits of yeast APC/C consist almost entirely of multiple repeats of the 34 amino acid tetratricopeptide residue (TPR) motif. These TPR subunits, Cdc16, Cdc27, Cdc23, and Apc5, mainly provide scaffolding and support to mediate other protein-protein interactions. Cdc27 and Cdc23 have been shown to support the binding of Cdc20 and Cdh1, as mutations in key residues of these subunits led to increased dissociation of the activators1. Apc10/Doc1, has been shown to promote substrate binding by mediating their interactions with Cdh1 and Cdc20.

The subunit Apc15 plays an important role in APC/CCdc20 activation following the bi-orientation of sister chromatids across the metaphase plate. When kinetochores are unattached to spindles, mitotic checkpoint complexes (MCC) and inhibit APC. In the absence of Apc15, MCCs and Cdc20 remain locked on the APC/C preventing its activity once the spindle checkpoint requirements are met. Apc15 mediates the turnover of Cdc20 and MCCs to provide information on the attachment state of kinetochores.