A lepidopteran orthologue of reaper reveals functional conservation and evolution of IAP antagonists.

Genetic studies in Drosophila melanogaster have revealed that IAP (Inhibitor of Apoptosis) proteins and IAP antagonists such as reaper play a pivotal role in controlling cell death in insects. Interestingly, while the sequences and structures of IAPs are highly conserved, the sequence of IAP antagonists diverged very rapidly during evolution, making their identification difficult. Using a customized bioinformatics approach, we identified an IAP antagonist, Ibm1, from the genome of the silkworm Bombyx mori. This is the first reaper/grim ortholog identified in a non-Dipteran insect. Previous analysis indicated that both Reaper and Grim induce cell death through their N-terminal IAP-binding motif (IBM) as well as the Grim_helix3 (GH3) domain. Functional studies indicated that Ibm1 binds to an IAP protein from Bombyx mori, BmIAP1, and induces apoptosis in insect cells via the IAP-binding motif, a 7 amino acid sequence that is highly conserved in all IAP antagonists. Interestingly, Ibm1 also contains a region that is a statistically significant match to the GH3 domain. Mutational analysis indicated that the GH3-like motif in Ibm1 has an important supportive role in IAP-antagonist function and can trigger cell death under certain conditions.