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Delta endotoxins (δ-endotoxins) are a family of
pore-forming toxin Pore-forming proteins (PFTs, also known as pore-forming toxins) are usually produced by bacteria, and include a number of protein exotoxins but may also be produced by other organisms such as apple snails that produce perivitellin-2 or earthw ...
s produced by ''
Bacillus thuringiensis ''Bacillus thuringiensis'' (or Bt) is a gram-positive bacteria, gram-positive, soil-dwelling bacterium, the most commonly used biological pesticide worldwide. ''B. thuringiensis'' also occurs naturally in the gut of caterpillars of various types ...
'' species of bacteria. They are useful for their
insecticidal Insecticides are pesticides used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. The major use of insecticides is in agriculture, but they are also used in home and garden settings, in ...
action and are the primary toxin produced by the genetically modified (GM) Bt maize/corn and other GM crops. During
spore In biology, a spore is a unit of sexual reproduction, sexual (in fungi) or asexual reproduction that may be adapted for biological dispersal, dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores fo ...
formation the bacteria produce crystals of such proteins (hence the name Cry toxins) that are also known as parasporal bodies, next to the
endospore An endospore is a dormant, tough, and non-reproductive structure produced by some bacteria in the phylum Bacillota. The name "endospore" is suggestive of a spore or seed-like form (''endo'' means 'within'), but it is not a true spore (i.e., not ...
s; as a result some members are known as a parasporin. The Cyt (cytolytic) toxin group is another group of delta-endotoxins formed in the cytoplasm. VIP toxins (vegetative insecticidal proteins) are formed at other stages of the life cycle.


Mechanism of action

When an insect ingests these proteins, they are activated by
proteolytic cleavage Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Protein degradation is a major regulatory mechanism of gene expression and contributes substantially to shaping mammalian proteomes. Uncatalysed, the hydrolysis o ...
. The N-terminus is cleaved in all of the proteins and a
C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...
extension is cleaved in some members. Once activated, the endotoxin binds to the gut
epithelium Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
and causes
cell lysis Lysis ( ; from Greek 'loosening') is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ' ...
by the formation of cation-selective channels, which leads to death. For many years there was no clarity as to the relationship between
aminopeptidase N Membrane alanyl aminopeptidase () also known as alanyl aminopeptidase (AAP) or aminopeptidase N (AP-N) is an enzyme that in humans is encoded by the ANPEP gene. Function Aminopeptidase N is located in the small-intestinal and renal microvill ...
and Bt toxins. Although AP-N does bind Cry proteins in vitro (reviewed by Soberón et al. 2009 and Pigott & Ellar 2007), 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 Lepidoptera ( ) or lepidopterans is an order (biology), order of winged insects which includes butterflies and moths. About 180,000 species of the Lepidoptera have been described, representing 10% of the total described species of living organ ...
examples. Subsequently, however Herrero et al. 2005 showed correlation between nonexpression and Bt resistance, and actual resistance was found in ''
Helicoverpa armigera ''Helicoverpa armigera'' is a species of Lepidoptera in the family Noctuidae. It is known as the cotton bollworm, corn earworm, Old World (African) bollworm, or scarce bordered straw (the lattermost in the UK, where it is a migrant). The larvae ...
'' by Zhang et al. 2009, in ''
Ostrinia nubilalis The European corn borer (''Ostrinia nubilalis''), also known as the European corn worm or European high-flyer, is a moth of the family Crambidae. It is a pest of grain, particularly maize (''Zea mays''). The insect is native to Europe, origina ...
'' by Khajuria et al. 2011, and in ''
Trichoplusia ni The cabbage looper (''Trichoplusia ni'') is a medium-sized moth in the family Noctuidae, a family commonly referred to as owlet moths. Its common name comes from its preferred host plants and distinctive crawling behavior. Cruciferous vegetable ...
'' by Baxter et al. 2011 and Tiewsiri & Wang 2011 (also all Lepidoptera). 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.


Structure

The activated region of the delta toxin is composed of three distinct
structural domain In molecular biology, a protein domain is a region of a protein's Peptide, polypeptide chain that is self-stabilizing and that Protein folding, folds independently from the rest. Each domain forms a compact folded Protein tertiary structure, thre ...
s: an
N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
helical bundle A helix bundle is a small protein fold composed of several alpha helices that are usually nearly parallel or antiparallel to each other. Three-helix bundles Three-helix bundles are among the smallest and fastest known cooperatively folding struct ...
domain () involved in membrane insertion and pore formation; a
beta-sheet The beta sheet (β-sheet, also β-pleated sheet) is a common structural motif, motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone chain, backbon ...
central domain involved in receptor binding; and a C-terminal
beta-sandwich Beta-sandwich or β-sandwich domains consisting of 80 to 350 amino acids occur commonly in proteins. They are characterized by two opposing antiparallel beta sheets (β-sheets). The number of strands found in such domains may differ from one prote ...
domain () that interacts with the N-terminal domain to form a channel.


Types

''B. thuringiensis'' encodes many proteins of the delta endotoxin family (), with some strains encoding multiple types simultaneously. A gene mostly found on
plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria and ...
s, delta-entotoxins sometimes show up in genomes of other species, albeit at a lower proportion than those found in ''B. thuringiensis''. The gene names looks like Cry3Bb, which in this case indicates a Cry toxin of superfamily 3 family B subfamily b. ''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. The Cyt toxins tend to form their own group distinct from Cry toxins. Not all ''Cry'' crystal-form toxins directly share a common root. 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. Specific delta-endotoxins that have been inserted with
genetic engineering Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of Genetic engineering techniques, technologies used to change the genet ...
include Cry3Bb1 found in MON 863 and Cry1Ab found in
MON 810 The MON 810 corn is a genetically modified maize used around the world. It is a ''Zea mays'' line known as YieldGard from the company Monsanto. This plant is a genetically modified organism (GMO) designed to combat crop loss due to insects. There ...
, 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. Other common toxins include Cry2Ab and Cry1F in
cotton Cotton (), first recorded in ancient India, is a soft, fluffy staple fiber that grows in a boll, or protective case, around the seeds of the cotton plants of the genus '' Gossypium'' in the mallow family Malvaceae. The fiber is almost pure ...
and maize/corn. In addition, Cry1Ac is effective as a vaccine adjuvant in humans. 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.


References


Further reading

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External links


Cry3Bb1
at the ''
United States Environmental Protection Agency The Environmental Protection Agency (EPA) is an independent agency of the United States government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it began operation on De ...
'' {{DEFAULTSORT:Delta Endotoxin Protein domains Peripheral membrane proteins Bacterial toxins Crystals Proteins