Positive cooperativity among insecticidal scorpion neurotoxins

Herrmann, Robert O.; Moskowitz, Haim; Zlotkin, Eliahu; Hammock, Bruce D.

doi:10.1016/0041-0101(95)98053-x

Cited by 47 publications

(20 citation statements)

References 16 publications

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“…However, co-injection of CSTX-1 and CSTX-9, both in toxic concentrations, increased the toxicity by more than 50% when compared with the theoretical toxicity sum of CSTX-1 and CSTX-9 injected alone, thus exhibiting a positive cooperativity. These findings are in agreement with other reports in which positive cooperativities between different neurotoxins were demonstrated by applying the components in a 1:1 molar ratio or in concentrations in which both components alone cause intoxications, or by using toxins from different sources (Bindokas et al, 1991;Herrmann et al, 1995;Shu and Liang, 1999;Regev et al, 2003;Adams, 2004).…”

Section: Interactions Between Peptidessupporting

confidence: 83%

Spider venom: enhancement of venom efficacy mediated by different synergistic strategies in Cupiennius salei

Wullschleger

Nentwig

Kuhn‐Nentwig

2005

Journal of Experimental Biology

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Besides the power of the chelicerae, synergistic interactions between different components in the venom of Cupiennius salei ensure the hunting success of this spider. The main components of the venom were tested alone or in combination according to their physiological venom concentrations in Drosophila bioassays. The high K + ion content of the venom synergistically increases the insecticidal activity of the neurotoxins CSTX-1, CSTX-9 and CSTX-13 by 20% but does not influence the insecticidal effectiveness of the antimicrobially and cytolytically acting cupiennin 1a. Histamine only enhances the activity of the main neurotoxin CSTX-1. An important role in the envenomation process is exhibited by cupiennin 1a, which increases the insecticidal activity of the abovementioned neurotoxins by up to 65%. Additionally, the highly synergistic effect of the enhancer CSTX-13 on CSTX-1, provoked in non-toxic physiological concentrations, could be verified for CSTX-9, but not for cupiennin 1a. CSTX-1 and CSTX-9 show positive interactions only when both are injected in toxic nonphysiological concentrations.

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Section: Interactions Between Peptidessupporting

confidence: 83%

Spider venom: enhancement of venom efficacy mediated by different synergistic strategies in Cupiennius salei

Wullschleger

Nentwig

Kuhn‐Nentwig

2005

Journal of Experimental Biology

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“…The uniqueness of Bj-xtrIT, compared with other excitatory toxins, seems to be of great importance and provides the following advantages: 1) amenability to genetic dissection and structural analysis due to the easy production and ability to fold in vitro; 2) distinction between conserved versus variable regions, which enables a mutagenic approach to determine functionally important residues; and 3) an applied potential arising from its prominent anti-lepidopteran toxicity (PU 50 ϭ 1.4 g/100 mg of body weight) compared with the effect (PU 50 ϭ 2.5 g/100 mg of body weight) induced by the classical excitatory toxin AaHIT (45). It is possible that the metabolic fate of Bj-xtrIT in the hemolymph differs from that of AaHIT with respect to accessibility barriers and to degradation processes.…”

Section: Discussionmentioning

confidence: 99%

The Putative Bioactive Surface of Insect-selective Scorpion Excitatory Neurotoxins

Froy

Zilberberg

Gordon

et al. 1999

Journal of Biological Chemistry

122

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Scorpion neurotoxins of the excitatory group show total specificity for insects and serve as invaluable probes for insect sodium channels. However, despite their significance and potential for application in insect-pest control, the structural basis for their bioactivity is still unknown. We isolated, characterized, and expressed an atypically long excitatory toxin, Bj-xtrIT, whose bioactive features resembled those of classical excitatory toxins, despite only 49% sequence identity. With the objective of clarifying the toxic site of this unique pharmacological group, Bj-xtrIT was employed in a genetic approach using point mutagenesis and biological and structural assays of the mutant products. A primary target for modification was the structurally unique C-terminal region. Sequential deletions of C-terminal residues suggested an inevitable significance of Ile 73 and Ile 74 for toxicity. Based on the bioactive role of the C-terminal region and a comparison of Bj-xtrIT with a Bj-xtrIT-based model of a classical excitatory toxin, AaHIT, a conserved surface comprising the C terminus is suggested to form the site of recognition with the sodium channel receptor.

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“…Enhancement of insecticidal efficacy through the cooperative interaction of different venom peptide neurotoxins in spiders (35) and scorpions (36,37) has been well investigated. Additionally, synergistic interactions between acylpolyamines and cysteine-rich peptide neurotoxins (38) as well as between cytolytic peptides and neurotoxins have been described (12)(13)(14).…”

Section: Biological Function Of Cstx-13 In the Venommentioning

confidence: 99%

CSTX-13, a highly synergistically acting two-chain neurotoxic enhancer in the venom of the spiderCupiennius salei(Ctenidae)

Wullschleger

Kuhn‐Nentwig

Tromp

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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The survival of the spider Cupiennius salei depends on its hunting success, which largely relies on its immediately paralyzing multicomponent venom. Here, we report on the isolation and characterization of CSTX-13, a neurotoxic enhancer in the spider venom. De novo elucidation of the disulfide bridge pattern of CSTX-13 and the neurotoxin CSTX-1 by tandem MS revealed an identical arrangement. However, in contrast to CSTX-1, CSTX-13 is a two-chain peptide with two interchain and two intrachain disulfide bridges. Furthermore, the insecticidal activity of CSTX-13 is synergistically increased in the presence of K ؉ ions as well as of the cytolytic peptide cupiennin 1a. We demonstrated that the weakly neurotoxic CSTX-13 enhances the paralytic activity of the neurotoxin CSTX-1 by 65% when it is administered with the latter at its entirely nontoxic physiological concentration, which is 440 times below its LD50 concentration.

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Positive cooperativity among insecticidal scorpion neurotoxins

Cited by 47 publications

References 16 publications

Spider venom: enhancement of venom efficacy mediated by different synergistic strategies in Cupiennius salei

Spider venom: enhancement of venom efficacy mediated by different synergistic strategies in Cupiennius salei

The Putative Bioactive Surface of Insect-selective Scorpion Excitatory Neurotoxins

CSTX-13, a highly synergistically acting two-chain neurotoxic enhancer in the venom of the spiderCupiennius salei(Ctenidae)

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