This entry represents DIABLO (Direct IAP-Binding protein with Low PI) proteins, also known as Smac (Second Mitochondria-derived Activator of Caspases) and and their homologues. DIABLO promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway, and by opposing the inhibitory activity of inhibitor of apoptosis proteins (XIAP-BIR3). The protein assumes an elongated three-helix bundle structure, and forms a dimer in solution [, ].
Smac (Second Mitochondria-derived Activator of Caspase) and DIABLO (Direct IAP-Binding protein with Low PI) are 29kDa mitochondrial precursor proteins. Apoptosis, or programmed cell death, is an essential process in metazoan development and homeostasis. Apoptosis is carried out by caspases, which are under tight regulatory control. Inhibitor-of-apoptosis proteins (IAP) suppress apoptosis by inhibiting caspases, while the mitochondrial protein Smac/Diablo promotes apoptosis by suppressing IAPs. The N-terminal four sequences in Smac/Diablo are responsible for the protein's interaction with IAPs []. The crystal structure of Smac/Diablo reveals a closed, three-helical bundle structure with a left-handed twist, and that the protein homodimerises through an extensive hydrophobic interface [].
