Programmed cell death or apoptosis is critical for development and homeostasis in metazoans. The inhibitor of apoptosis (IAP) proteins antagonize cell death by suppressing active caspases. This inhibition can be reversed by IAP antagonists Reaper, Grim, and Hid in flies and the second mitochondrial-derived activator of caspase (Smac)/Diablo family of proteins in vertebrates. Despite their well known anti-death function in vitro, IAPs have not been shown to be required for apoptosis inhibition in vertebrate development. Gene ablation of baculoviral IAP repeat-containing (Birc)4 (XIAP), the most potent caspase inhibitory IAP in cultured cells, does not perturb mouse development. Birc6 (Bruce) is a large mouse IAP with a molecular mass of 528 kDa (13). Similar to other IAPs, Bruce promotes cell survival. It inhibits apoptosis by binding to caspases through its BIR domain, and its caspase inhibitory activity also requires the C-terminal UBC domain. Because Bruce is a chimeric E2/E3 ubiquitin ligase and can ubiquitylate Smac/Diablo and active caspase-9 in vitro. Bruce is thought to preserve cell survival by antagonizing apoptosis induced by spontaneously released Smac. Here you can see a detailed view of the cryo-EM structure of helical arch of BIRC6 (PDB code: 8E2E)

#molecularart ... #immolecular ... #apoptosis ... #helical ... #arch ... #bruce ... #birc6 ... #cryoem

Structure rendered with @proteinimaging and depicted with @corelphotopaint