To produce its lethal effect the δ-endotoxin need to be eaten by the target insect and reach its midgut . Upon ingestion, the Bt protoxin is dissolved and enzymatically activated by the insect’s midgut proteases such as trypsin and chymotrypsin, to produce an activated toxin. After penetration of the peritrophic membrane (domain I), the domain II of the toxin binds with high affinity to specific receptors such as aminopeptidase or cadherin on the brush border membrane of the midgut. Such binding triggers a conformational change of the toxin to make non-selective pores with two hypothetical models: the Penknife and the Umbrella models.
The Penknife model proposes that the α-helices α5 and α6 of the domain I flip into the membrane as a helical hairpin, while the Umbrella model hypothesizes that the helices α4 and α5 drop down into the plasma membrane surface with their hydrophobic faces toward the membrane (Knowles, 1994). In both models, the formed channels interfere with ion transport allowing large influx of K+ and efflux of H+, that will lead to osmotic absorption of water by insect cells. This will cause the swelling and lysis of cells of the insect, which will stop feeding. At this point the normal midgut bacteria enter the ruptured cells and invade the whole body, ultimately leading to the death of the insect by septicemia(Broderick et al. 2006)