The linker region preceding BIR2 of XIAP is responsible for the inhibition of caspase-3 and -7, which is further stabilized by interaction with the BIR2 domain itself (Scott et al. 2005). Binding of DIABLO (SMAC) to BIR2 domain of XIAP can destabillize the XIAP:CASP3 interaction promoting the liberation of active caspase-3 from its complex with XIAP (Kashkar et al. 2003). Furthermore, SMAC (DIABLO) interacted with the BIR3 and then BIR2 domains of XIAP sequentially, and such dynamic interaction cooperatively neutralized inhibition of caspase-3 by the linker region of XIAP (Gao Z et al. 2007).