A mechanistic insight into caspase-7 inhibition by BIR1-2 domains of XIAP and cIAP1

作者：Bagheri S; Davoodi J; Saboury A A^*; Salmanian A H

来源：Journal of the Iranian Chemical Society, 2012, 9(5): 615-623.

DOI：10.1007/s13738-012-0076-5

• Apoptosis
• IAP
• BIR1
• BIR2
• Inhibition mechanism
• Circular dichroism spectroscopy

Previous studies failed to demonstrate any role for the BIR1 domain of the inhibitor of apoptosis proteins (IAPs) in inhibition of executioner caspases. In this study, XIAP-BIR1-2 and c-IAP1-BIR1-2 domains have been used to investigate the role of BIR1 in the inhibition of caspase-7. Kinetic analysis confirmed that caspase-7 was inhibited in an uncompetitive manner at lower concentrations of XIAP-BIR1-2, whereas the inhibition was switched to the mixed type mode at higher concentrations of the inhibitor. In contrast, cIAP1-BIR1-2 inhibited caspase-7 in a mixed type mode at all examined concentrations. These data suggest that the presence of BIR1 is essential for inhibition of caspase-7 by cIAP1. Far-UV CD and fluorescence spectroscopy experiments showed that despite similar secondary structures, XIAP-BIR1-2 and cIAP1-BIR1-2 have different biophysical properties. BIR1-2 domain of XIAP was found to be more flexible than cIAP1, which may be the reason behind differences in their kinetic properties.

• 出版日期2012-10