Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides

The inhibitor of apoptosis protein DIAP1 suppresses apoptosis in Drosophila , with the second BIR domain (BIR2) playing an important role. Three protei ns, Hid, Grim, and Reaper, promote apoptosis, in part by binding to DIAP1 t hrough their conserved N-terminal sequences. The crystal structures of DIAP 1-BIR2 by itself and in complex with the N-terminal peptides from Hid and G rim reveal that these peptides bind a surface groove on DIAP1, with the fir st four amino acids mimicking the binding of the Smac tetrapeptide to XIAP. The next 3 residues also contribute to binding through hydrophobic interac tions. Interestingly, peptide binding induces the formation of an additiona l alpha helix in DIAP1. Our study reveals the structural conservation and d iversity necessary for the binding of IAPs by the Drosophila Hid/Grim/Reape r and the mammalian Smac proteins.