Which component of the Mitotic Checkpoint Complex (MCC) directly inhibits APC/C?
Mitotic checkpoint complex inhibition of anaphase-promoting complex relies on multiple contacts that block substrate recognition and catalytic activity. MCC consists of BubR1, Bub3, Mad2, and Cdc20, assembled at unattached kinetochores. Closed conformer of Mad2, generated through Mad1-Mad2 template mechanism, wraps around Cdc20 as safety belt, sequestering it and presenting inhibitory surface. Although BubR1 contains KEN boxes that mimic APC/C substrates and directly blocks substrate binding via pseudo-substrate inhibition, Mad2 provides crucial initial locking of Cdc20 in MCC, preventing it f
Ref: Alfieri et al., Nature 2016, APC/C-MCC Structure; De Antoni et al., Curr Biol 2005, Mad2 Conformers.