Stable Identifier
Reaction [binding]
Homo sapiens
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Second mitochondria derived activator of caspase/direct inhibitor of apoptosis binding protein with low pI (SMAC, also known as DIABLO) is normally a mitochondrial protein but is released into the cytosol when cells undergo apoptosis (Du C et al. 2000). Mitochondrial import and cleavage of its signal peptide are required for SMAC to gain its apoptotic activity (Du C et al. 2000). In vitro studies revealed that dimerization was required for its function, while monomerization of cytosolic mature SMAC attenuated interaction with XIAP (Chai J et al. 2000; Burke SP & Smith JB 2010). Moreover, SMAC dimer showed high stability in vitro as measured by high hydrostatic pressure, low and high temperatures, and chemical denaturation (Goncalves RB et al. 2008). Binding of SMAC (DIABLO) to the BIR3 region of X linked inhibitor of apoptosis protein (XIAP) competitively inhibits binding of XIAP to caspase 9, while binding to the BIR2 region sterically hinders the interaction of XIAP with CASP3 and CASP7 (Srinivasula SM et al. 2001; Abhari BA & Davoodi J 2008).
Literature References
PubMed ID Title Journal Year
11140638 Structural basis of IAP recognition by Smac/DIABLO

Chai, J, Suber, TL, Wang, X, Shi, Y, Wu, JW, Du, C, Wu, G

Nature 2000
11257231 Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain

Huang, Y, Wu, H, Rich, RL, Park, YC, Myszka, DG, Segal, D

Cell 2001
11242052 A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis

Alnemri, ES, Chai, J, Lee, RA, Hegde, R, Shi, Y, Robbins, PD, Saleh, A, Srinivasula, SM, Fernandes-Alnemri, T, Shiozaki, E, Datta, P

Nature 2001
10972280 Structural and biochemical basis of apoptotic activation by Smac/DIABLO

Chai, J, Wang, X, Shi, Y, Wu, JW, Du, C, Kyin, S

Nature 2000
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