Delta endotoxin

When an insect ingests these proteins, they are activated by proteolytic cleavage. The N-terminus is cleaved in all of the proteins and a C-terminal extension is cleaved in some members. Once activated, the endotoxin binds to the gut epithelium and causes cell lysis by the formation of cation-selective channels, which leads to death.[2][1]

For many years there was no clarity as to the relationship between aminopeptidase N and Bt toxins. Although AP-N does bind Cry proteins in vitro[3] (reviewed by Soberón et al. 2009[4] and Pigott & Ellar 2007[5]),[6] no cases of resistance – or even reduced in vitro binding – due to AP-N structure alteration were known through 2002, and there was some doubt that the resistance mechanism was so straight forward. Indeed, Luo et al. 1997, Mohammed et al. 1996, and Zhu et al. 2000 positively found this to not occur in Lepidoptera examples.[3] Subsequently, however Herrero et al. 2005 showed correlation between nonexpression and Bt resistance,[6] and actual resistance was found in Helicoverpa armigera by Zhang et al. 2009,[6][7] in Ostrinia nubilalis by Khajuria et al. 2011, and in Trichoplusia ni by Baxter et al. 2011 and Tiewsiri & Wang 2011 (also all Lepidoptera).[6] There continues to be confirmation that AP-Ns do not by themselves affect resistance in some cases, possibly due to sequential binding by the toxin being required to produce its effect. In this sequence each binding step is theoretically not indispensable, but if it occurs does contribute to the final pore formation result.[7]

The activated region of the delta toxin is composed of three distinct structural domains: an N-terminal helical bundle domain (InterPro: IPR005639) involved in membrane insertion and pore formation; a beta-sheet central domain involved in receptor binding; and a C-terminal beta-sandwich domain (InterPro: IPR005638) that interacts with the N-terminal domain to form a channel.[1][2]

B. thuringiensis encodes many proteins of the delta endotoxin family (InterPro: IPR038979), with some strains encoding multiple types simultaneously.[8] A gene mostly found on plasmids,[9] delta-entotoxins sometimes show up in genomes of other species, albeit at a lower proportion than those found in B. thuringiensis.[10] The gene names looks like Cry3Bb, which in this case indicates a Cry toxin of superfamily 3 family B subfamily b.[11]

Cry proteins that are interesting to cancer research are listed under a parasporin (PS) nomenclature in addition to the Cry nomenclature. They do not kill insects, but instead kill leukemia cells.[12][13][14] The Cyt toxins tend to form their own group distinct from Cry toxins.[15] Not all Cry — crystal-form — toxins directly share a common root.[16] Examples of non-three-domain toxins that nevertheless have a Cry name include Cry34/35Ab1 and related beta-sandwich binary (Bin-like) toxins, Cry6Aa, and many beta-sandwich parasporins.[17]

Specific delta-endotoxins that have been inserted with genetic engineering include Cry3Bb1 found in MON 863 and Cry1Ab found in MON 810, both of which are maize/corn cultivars. Cry3Bb1 is particularly useful because it kills Coleopteran insects such as the corn rootworm, an activity not seen in other Cry proteins.[1] Other common toxins include Cry2Ab and Cry1F in cotton and maize/corn.[18] In addition, Cry1Ac is effective as a vaccine adjuvant in humans.[19]

Some insects populations have started to develop resistance towards delta endotoxin, with five resistant species found as of 2013. Plants with two kinds of delta endotoxins tend to make resistance happen slower, as the insects have to evolve to overcome both toxins at once. Planting non-Bt plants with the resistant plants will reduce the selection pressure for developing the toxin. Finally, two-toxin plants should not be planted with one-toxin plants, as one-toxin plants act as a stepping stone for adaption in this case.[18]

• Cry3Bb1 at the United States Environmental Protection Agency