NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP.

摘要: The inhibitor-of-apoptosis (IAP) family of proteins, originally identified in baculoviruses1, regulate programmed cell death a variety organisms2,3,4,5,6. IAPs inhibit specific enzymes (caspases) the cascade7,8,9,10,11 and contain one to three modules common 70-amino-acid motif called BIR domain12. Here we describe nuclear magnetic resonance structure region encompassing second domain (BIR2) human IAP member, XIAP (also hILP or MIHA). consists three-stranded antiparallel β-sheet four α-helices resembles classical zinc finger13. Unexpectedly, conserved amino acids within linker between BIR1 BIR2 domains were found be critical for inhibiting caspase-3. absence presence these residues may explain differences caspase inhibition observed different truncated full-length IAPs10,11. Our data further indicate that bind active site interact with an adjacent on enzyme.