Binding of <i>Bacillus thuringiensis</i> Cry1Ac toxin to <i>Manduca sexta</i> aminopeptidase‐N receptor is not directly related to toxicity

Jenkins, Jeremy L.; Lee, Mi Kyong; Sangadala, Sreedhara; Adang, Michael J.; Dean, Donald H.

doi:10.1016/s0014-5793(99)01559-8

Cited by 57 publications

(53 citation statements)

References 37 publications

(45 reference statements)

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“…The biochemical process of membrane insertion is not completely understood. There is evidence that some Cry proteins have multiple receptors, or may bind to multiple sites on a single receptor and it has been demonstrated that receptor binding is necessary but not sufficient for toxicity (Aronson and Shai, 2001;Jenkins et al, 1999;OECD, 2007). There is some evidence based partly on experiments using sublethal concentrations, that there may be other relevant interactions between Cry proteins and their insect targets (Aronson and Shai, 2001;Zhang et al, 2006).…”

Section: Mechanism Of Cry1ac Insecticidal Activitymentioning

confidence: 99%

A review of the environmental safety of the Cry1Ac protein

Lean¹

2011

Environ. Biosafety Res.

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1 Event refers to a single transformation event: the incorporation of a transgene into a plant genome. A single transformation event can be crossed into multiple lines.2 Tomato Event 5345 expressing Cry1Ac was deregulated by USDA APHIS but never received registration as a pesticide with the USEPA and was not commercialized anywhere in the world. It will not be considered elsewhere in this paper. 3 This includes approvals for lines generated through breeding and transformation with additional transgenes.

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Section: Mechanism Of Cry1ac Insecticidal Activitymentioning

confidence: 99%

A review of the environmental safety of the Cry1Ac protein

Lean¹

2011

Environ. Biosafety Res.

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“…However, a glycosylphosphatidylinositol-anchored alkaline phosphatase protein has been also recognized as a Cry1Ac receptor in Heliothis virescens and M. sexta (7,8). This receptor could also participate in facilitating pore membrane insertion potentially explaining why Cry1Ac toxin mutations that were severely affected in aminopeptidase binding were still active against M. sexta larvae (19,20). In this model, the pre-pore oligomer is responsible for initiating cell death.…”

Section: Bacillus Thuringiensis (Bt)mentioning

confidence: 99%

Bacillus thuringiensis Cry1Ab Mutants Affecting Oligomer Formation Are Non-toxic to Manduca sexta Larvae

Jiménez-Juárez

Muñóz-Garay

Gómez

et al. 2007

Journal of Biological Chemistry

102

108

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Pore-forming toxins are biological weapons produced by a variety of living organisms, particularly bacteria but also by insects, reptiles, and invertebrates. These proteins affect the cell membrane of their target, disrupting permeability and leading eventually to cell death. The pore-forming toxins typically transform from soluble, monomeric proteins to oligomers that form transmembrane channels. The Cry toxins produced by Bacillus thuringiensis are widely used as insecticides. These proteins have been recognized as pore-forming toxins, and their primary action is to lyse midgut epithelial cells in their target insect. To exert their toxic effect, a prepore oligomeric intermediate is formed leading finally to membrane-inserted oligomeric pores. To understand the role of Cry oligomeric pre-pore formation in the insecticidal activity we isolated point mutations that affected toxin oligomerization but not their binding with the cadherin-like, Bt-R 1 receptor. We show the helix ␣-3 in domain I contains sequences that could form coiled-coil structures important for oligomerization. Some single point mutants in this helix bound Bt-R 1 receptors with similar affinity as the wild-type toxin, but were affected in oligomerization and were severally impaired in pore formation and toxicity against Manduca sexta larvae. These data indicate the pre-pore oligomer and the toxin pore formation play a major role in the intoxication process of Cry1Ab toxin in insect larvae. Bacillus thuringiensis (Bt)2 is a Gram-positive bacterium that produces insecticidal Cry toxins. Cry proteins are widely used for insect control in agriculture and forestry and against mosquitoes, due to their high specificity and safety for humans and for the environment (1, 2).Although Bt Cry toxins are widely used as insecticides their mode of action is still not completely understood. These Cry toxins are pore-forming toxins that induce cell death by forming ionic pores following insertion into the membrane, causing osmotic lysis of larvae midgut cells (1-3). However, recently an alternative model proposed that these toxins activate a signal pathway through Bt-R 1 receptor interaction, which results in insect cell death without the participation of lytic pores into the membrane (4). It is important to note that this alternative model was proposed based on the effect of Cry1Ab toxin to cultured Trichoplusia ni H5 insect cells expressing the Manduca sexta toxin receptor, Bt-R 1 .Nevertheless, in both models, receptor interaction with exposed regions in domains II and III of Cry1A toxins (1-4) is a key step that determines insect toxicity. In the case of Cry1A toxins, two receptors have been characterized in several lepidopteran species: cadherin-like proteins, known as Bt-R receptors (5) (Bt-R 1 in the case of M. sexta), and glycosylphosphatidylinositol-anchored proteins, as aminopeptidase-N or alkaline phosphatase (6, 7).In the pore-forming model, it is proposed that both receptors are important and participate in a sequential manner (3,8,9). After proteoly...

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“…Importantly, another GPI-anchored protein, an alkaline phosphatase, has been recognized as a Cry1Ac receptor in Heliothis virescens and M. sexta [22,23]. Alkaline phosphatase could also participate in facilitating the pre-pore membrane insertion into lipid rafts, explaining why Cry1Ac toxin mutations that were severely affected in APN binding are still active against M. sexta larvae [6,20]. In the pore forming model, the pre-pore oligomer is responsible for initiating cell death [3].…”

Section: Models Of the Mode Of Action Of Cry Toxins In Lepidopteran Imentioning

confidence: 99%

The pre-pore from Bacillus thuringiensis Cry1Ab toxin is necessary to induce insect death in Manduca sexta

et al. 2008

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The insecticidal Cry toxins from Bacillus thuringiensis bacteria are pore-forming toxins that lyse midgut epithelial cells in insects. We have previously proposed that they form pre-pore oligomeric intermediates before membrane insertion.For formation of these oligomers coiled-coil structures are important, and helix α-3 from Cry toxins could form coiled-coils. Our data shows that different mutations in helix α-3 are affected in pore formation and toxicity. Mutants affected in toxicity bind Bt-R 1 receptor with a similar K D as the wild type toxin but do not form oligomers nor induce pore formation in planar lipid bilayers, indicating that the pre-pore oligomer is an obligate intermediate in the intoxication of Cry1Ab toxin and that interaction of monomeric Cry1Ab with Bt-R 1 is not enough to kill susceptible larvae.

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Binding of Bacillus thuringiensis Cry1Ac toxin to Manduca sexta aminopeptidase‐N receptor is not directly related to toxicity

Cited by 57 publications

References 37 publications

A review of the environmental safety of the Cry1Ac protein

A review of the environmental safety of the Cry1Ac protein

Bacillus thuringiensis Cry1Ab Mutants Affecting Oligomer Formation Are Non-toxic to Manduca sexta Larvae

The pre-pore from Bacillus thuringiensis Cry1Ab toxin is necessary to induce insect death in Manduca sexta

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