Crystallization of the<i>Bacillus thuringiensis</i>toxin Cry1Ac and its complex with the receptor ligand<i>N</i>-acetyl-<scp>D</scp>-galactosamine

Derbyshire, D.J.; Ellar, David J.; Li, Jade

doi:10.1107/s090744490101040x

Cited by 51 publications

(49 citation statements)

References 24 publications

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“…Domain III shows less structural variability than domain II, and the main differences are found in the lengths, orientations, and sequences of the loops (11). The importance of these differences is particularly evident with Cry1Aa and Cry1Ac, where a loop extension in Cry1Ac creates a unique N-acetylgalactosamine (GalNAc) binding pocket implicated in receptor binding (21,32,108). Domain III has been compared to a number of different proteins (28), but its similarity to carbohydrate-binding modules (CBMs) found in microbial glycoside hydrolases, lyases, and esterases is particularly striking.…”

Section: Toxin Structure and Functionmentioning

confidence: 99%

“…Jenkins et al showed that mutants with alanine substitutions at Q509, R511, Y513, or 509 QNR 511 failed to bind to purified M. sexta APN (81) and bound to purified L. dispar APN with lower affinity (82). The crystal structure of Cry1Ac, solved in the presence and absence of GalNAc, has helped to further characterize the domain III APN binding site and has provided a structural explanation for why Cry1Ac, but not Cry1Aa, binds to APN in a manner dependent on GalNAc (32,108). Analysis of the structure revealed a unique 6-residue insertion ( 505 GNNIQ N 510 ) in domain III that was not observed in Cry1Aa and was not predicted by an automatically generated model of Cry1Ac (81).…”

Section: Other Receptorsmentioning

confidence: 99%

“…To date, seven structures have been solved by X-ray crystallography: Cry1Aa (64), Cry1Ac (32,108), Cry2Aa (127), Cry3Aa (109), Cry3Ba (45), Cry4Aa (12), and Cry4Ba (11). These toxins show considerable differences in their amino acid sequences and insect specificity but, remarkably, they all have highly similar three domain structures (Table 1; Fig.…”

Section: Toxin Structure and Functionmentioning

confidence: 99%

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Role of Receptors in Bacillus thuringiensis Crystal Toxin Activity

Pigott

Ellar

2007

Microbiol Mol Biol Rev

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602

598

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SUMMARY Bacillus thuringiensis produces crystalline protein inclusions with insecticidal or nematocidal properties. These crystal (Cry) proteins determine a particular strain's toxicity profile. Transgenic crops expressing one or more recombinant Cry toxins have become agriculturally important. Individual Cry toxins are usually toxic to only a few species within an order, and receptors on midgut epithelial cells have been shown to be critical determinants of Cry specificity. The best characterized of these receptors have been identified for lepidopterans, and two major receptor classes have emerged: the aminopeptidase N (APN) receptors and the cadherin-like receptors. Currently, 38 different APNs have been reported for 12 different lepidopterans. Each APN belongs to one of five groups that have unique structural features and Cry-binding properties. While 17 different APNs have been reported to bind to Cry toxins, only 2 have been shown to mediate toxin susceptibly in vivo. In contrast, several cadherin-like proteins bind to Cry toxins and confer toxin susceptibility in vitro, and disruption of the cadherin gene has been associated with toxin resistance. Nonetheless, only a small subset of the lepidopteran-specific Cry toxins has been shown to interact with cadherin-like proteins. This review analyzes the interactions between Cry toxins and their receptors, focusing on the identification and validation of receptors, the molecular basis for receptor recognition, the role of the receptor in resistant insects, and proposed models to explain the sequence of events at the cell surface by which receptor binding leads to cell death.

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Section: Toxin Structure and Functionmentioning

confidence: 99%

Section: Other Receptorsmentioning

confidence: 99%

Section: Toxin Structure and Functionmentioning

confidence: 99%

See 1 more Smart Citation

Role of Receptors in Bacillus thuringiensis Crystal Toxin Activity

Pigott

Ellar

2007

Microbiol Mol Biol Rev

Self Cite

602

598

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“…While the Cry1Ac toxin lacks ester bonds there are nevertheless biochemical mechanisms mediated by glycan interactions by which it could bind to esterases as proposed by Gunning et al 69,78) Cry1Ac is known to have high affinity for N-acetyl galactosamine (GalNAc) moieties on proteins 80) and indeed the mechanism of action of the toxin is believed to involve its binding to GalNAc moieties on aminopeptidases which are localised to the larval gut wall via glycosylphosphotidylinositol (GPI) anchors. 81) Sublethal doses of Cry1Ac are also known to lead to the specific shedding and excretion of GPI-anchored proteins from lepidopteran larval guts.…”

Section: Heliothine Resistance To Other Insecticidesmentioning

confidence: 99%

Esterase-based metabolic resistance to insecticides in heliothine and spodopteran pests

Farnsworth

Teese

Yuan

et al. 2010

Journal of Pesticide Science

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IntroductionCarboxylesterases have been implicated in metabolic resistance to several classes of insecticide in a wide variety of pest insect species. [1][2][3] The classes most commonly involved are synthetic pyrethroids (SPs) and organophosphates (OPs), and carbamates (CBs) are also involved in several cases. There are also occasional reports of carboxylesterase phenotypes associated with resistance to benzoylureas, the oxadiazine indoxacarb, the diacylhydrazine tebufenozide, the organochlorine endosulfan and the proteinaceous Cry1Ac toxin of Bacillus thuringiensis that is expressed in transgenic crops. Figure 1 gives structures for some key compounds among these various classes of insecticide.It might be expected that carboxylesterases would be involved in SP resistance because the great majority of SPs are carboxylesters. However, no precise molecular mechanisms for esterase-based SP resistance have yet been elucidated in any insect. OPs are generally phosphotriesters rather than carboxylesters but nevertheless they bind many carboxylesterases with high affinity and this provides a basis for two forms of resistance, both now elucidated at a molecular level in several species. One form involves substantial overexpression of the esterase, allowing for effective sequestration of the insecticide. The other involves specific mutations in the active site of the enzyme which convert it to an OP hydrolase (the so-called "mutant ali-esterase" mechanism). CBs are carbamic acid (NH 2 COOH) derivatives, in which a functional group has been added as an ester; these esters are chemically similar to carboxylesters. Carbamates bind carboxylesterases with quite high affinity, but as yet the molecular mechanisms by which a (mutant) carboxylesterase confers CB resistance have not been elucidated in any species. Of the other insecticide classes occasionally linked to esterase-based resistance only indoxacarb has ester bonds (two Elevated esterase activities and increased band intensities of multiple esterase isozymes after electrophoresis are commonly associated with resistance to organophosphate, pyrethroid and carbamate insecticides in various heliothine and spodopteran pests. One possible explanation for this involves a 'master regulator' mutation in a more general chemical stress response. An association between elevated esterase activities and isozyme intensities has also been reported for resistance to the Cry1Ac toxin of Helicoverpa armigera. The basis for this is unclear albeit some involvement of esterases could be mediated by the toxin's affinity for N-acetyl galactosamine glycans on certain gut-expressed esterases in this species.

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“…To date, the X-ray crystal structures of several Cry dendotoxins Cry3Aa [12], Cry1Aa [13], Cry1Ac [36], Cry2Aa [37] and Cry3Bb [38] have been elucidated. Although these Cry toxins exert their specific toxicity against different target insect larvae, they display a high degree of overall 3D structural similarity, consisting of three distinct domains.…”

Section: D Structure and Functional Prediction Of Cry1i And Cry3a Prmentioning

confidence: 99%

Insilico Structural 3D Modelling of Novel Cry1Ib9 and Cry3A Toxins from Local Isolates of Bacillus thuringiensis

2013

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Three-dimensional (3D) models for the 79.2 kDa activated Cry1Ib9 and 77.4 kDa activated Cry3A d-endotoxins from Bacillus thuringiensis (Bt) native isolates that are specifically toxic to Coleopteran insect pests were constructed by utilizing homology modeling online tool. Evidences presented here, based on the identification of structural equivalent residues of Cry1Ib9 and Cry3A toxin through homology modelling indicate that, they share a common Bt toxin tridimensional structure. The main differences observed in Cry1I9 domain I at positions a2b (S56-I60), a4 (F78-l93) and additionally b0 (Q10-L12), a8a (T280-V282) were observed, in domain II at positions a9b (P333-L339), b6(T390-Q393), b7(V398-W404), b8 (V418-W425), b9 (E453-N454), b10 (S470-I479) where as in domain III the changes were observed at positions b19 (R601-F607), b20 (609-L613), b21 (S618-F627) and a11a (K655-F664), a13, a14 components present at downstream sites, where as in Cry3A main differences observed in domain I is at the position of a4 (P105-I152), a5 (Q163-A185), b1A(E190-L192), a6 (F193-Y217), Domain II is not consevered and main variations were observed at b2 (E292-L295), b3

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Crystallization of theBacillus thuringiensistoxin Cry1Ac and its complex with the receptor ligandN-acetyl-D-galactosamine

Cited by 51 publications

References 24 publications

Role of Receptors in Bacillus thuringiensis Crystal Toxin Activity

Role of Receptors in Bacillus thuringiensis Crystal Toxin Activity

Esterase-based metabolic resistance to insecticides in heliothine and spodopteran pests

Insilico Structural 3D Modelling of Novel Cry1Ib9 and Cry3A Toxins from Local Isolates of Bacillus thuringiensis

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