BotIT6

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BotIT6 is a toxin that binds to insect voltage gated sodium channels. It decreases the amplitude of the action potential, leading to paralysis.

Contents

Etymology and Source

BotIT6 is a neurotoxin produced by the common European scorpion, which is also known as the Buthus occitanus tunetanus. It is therefore appropriately named buthus occitanus tunetanus insect toxin 6 (BotIT6). [1] [2]

Chemistry

Structure BotIT6 consists of 62 amino-acids and has an experimentally determined molecular mass of 7260.84 Da. [1] [2]

N'-DGYPKQKNGCKYDCIINNKWCNGIC-KMHGGYGGYCWG-WGLACWC-EGLP-EDKKWWYETN-K-CGR-C'
The amino-acid sequence of BotIT6 [1]

Family

BotIT6 belongs to the Buthidae neurotoxin family. The toxins can be divided into groups based on their target animal. BotIT6 is targeted at insects. Toxins directed against insects, the main target being the sodium channels, can be divided into four groups, namely excitatory toxins, depressant toxins, α-type toxins and a group affecting both mammals and insects. [1] [3] Each group causes paralysis, albeit via different mechanisms. The BotIT6 has characteristics of depressant, excitatory and α subgroups. [1]

Homology

From an evolutionary perspective BotIT6 is linked to both the depressant and the α group. [1] BotIT6 is similar to depressant insect toxins, but also has similarities to α type and excitatory toxins. BotIT6 shares 58-66% of its amino-acid sequence with depressant insect toxins, and 24-34% with alfa type and excitatory toxins. In addition, it shares functional characteristics with all three groups. This has led to the hypothesis that BotIT6 could be an ancestral depressant toxin. [1]

Target

BotIT6 is directed specifically against insect voltage-gated sodium channels. There are no known mammalian sodium channels affected by BotIT6. [1] [2]

Mode of action

The exact mechanism of BotIT6 is still unclear. The neuropeptide binds to site 4 of voltage-gated sodium channels. [1] [4] The membrane of the axon is likely to be depolarized. Next, the sodium current is slowed down by BotIT6, which decreases the amplitude of the action potential. Eventually these events lead to paralysis. [1] In artificial environments the effect of BotIT6 is less potent than it is in vivo, which might be explained by other toxic neuropeptides in the venom of the scorpion. [2] These neuropeptide toxins may cooperate to make venom more effective. [5] Another possibility is the presence of other more potent toxins in the venom. [1] These toxins often share many characteristics, which means they partially overlap in binding sites. BotIT6 is known to compete with other neurotoxins, I-AaHIT and I-BotIT2, over the same binding site on the sodium channels for these toxins. [1] [6]

Toxicity

Bot1T6 is a positively charged basic structure. [1] [2] Basic toxins are usually more potent than acidic ones. [7] In addition, within the Buthidae neurotoxin family toxins, a higher total positive charge leads to a more toxic neuropeptide . [1] [7] These characteristics contribute in making Bot1T6 a very effective insect toxin. For cockroaches for instance, the LD50 was 10 ng/100 mg. Amongst other things this toxin leads to different forms of paralysis and uncoordinated motion. Although paralysis can sometimes be reversed but death can also occur without any previous warning symptoms. These effects occur only in insects. [1] [2]

Possible use

The possible effects of BotIT6 on mammals, when ingested per os, are still unclear. However, it is unlikely mammals would be harmed using this toxin, as BotIT6 is insect sodium channel specific. This makes BotIT6 a possible candidate for agricultural use as an insecticide. [2]

Related Research Articles

<span class="mw-page-title-main">Poneratoxin</span> Paralyzing neurotoxic peptide

Poneratoxin is a paralyzing neurotoxic peptide made by the bullet ant Paraponera clavata. It prevents inactivation of voltage gated sodium channels and therefore blocks synaptic transmission in the central nervous system. Specifically, poneratoxin acts on voltage gated sodium channels in skeletal muscle fibers, causing paralysis, and nociceptive fibers, causing pain. It is rated as a 4 plus on the Schmidt sting pain index, the highest possible rating with that system, and its effects can cause waves of pain up to twelve hours after a single sting. It is additionally being studied for its uses in biological insecticides.

Tityustoxin is a toxin found in the venom of scorpions from the subfamily Tityinae. By binding to voltage-dependent sodium ion channels and potassium channels, they cause sialorrhea, lacrimation and rhinorrhea.

<span class="mw-page-title-main">Scorpion toxin</span>

Scorpion toxins are proteins found in the venom of scorpions. Their toxic effect may be mammal- or insect-specific and acts by binding with varying degrees of specificity to members of the Voltage-gated ion channel superfamily; specifically, voltage-gated sodium channels, voltage-gated potassium channels, and Transient Receptor Potential (TRP) channels. The result of this action is to activate or inhibit the action of these channels in the nervous and cardiac organ systems. For instance, α-scorpion toxins MeuNaTxα-12 and MeuNaTxα-13 from Mesobuthus eupeus are neurotoxins that target voltage-gated Na+ channels (Navs), inhibiting fast inactivation. In vivo assays of MeuNaTxα-12 and MeuNaTxα-13 effects on mammalian and insect Navs show differential potency. These recombinants exhibit their preferential affinity for mammalian and insect Na+ channels at the α-like toxins' active site, site 3, in order to inactivate the cell membrane depolarization faster[6]. The varying sensitivity of different Navs to MeuNaTxα-12 and MeuNaTxα-13 may be dependent on the substitution of a conserved Valine residue for a Phenylalanine residue at position 1630 of the LD4:S3-S4 subunit or due to various changes in residues in the LD4:S5-S6 subunit of the Navs. Ultimately, these actions can serve the purpose of warding off predators by causing pain or to subdue predators.

Pompilidotoxins (PMTXs) are toxic substances that can only be found in the venom of several solitary wasps. This kind of wasp uses their venom to offensively capture prey and is relatively harmless to humans. This is in stark contrast to social insects that defend themselves and their colonies with their venom.

Birtoxin is a neurotoxin from the venom of the South African Spitting scorpion. By changing sodium channel activation, the toxin promotes spontaneous and repetitive firing much like pyrethroid insecticides do

Bestoxin is a neurotoxin from the venom of the South African spitting scorpion Parabuthus transvaalicus. Most likely, it targets sodium channel function, thus promoting spontaneous and repetitive neuronal firing. Following injection into mice, it causes non-lethal writhing behaviour.

BmKAEP is a neurotoxin from the venom of the Manchurian scorpion (Mesobuthus martensii). It is a β-toxin, which shift the activation voltage of sodium channels towards more negative potentials.

<i>Mesobuthus eupeus</i> Species of scorpion

Mesobuthus eupeus is a polymorphic scorpion species belonging to the well-known family Buthidae. Commonly known as the lesser Asian scorpion or the mottled scorpion. It is thought to be the most widely dispersed species of the genus Mesobuthus, perhaps even of the family Buthidae.

Bukatoxin is an α-scorpion toxin found in the venom of the Chinese scorpion Buthus martensi Karsch. By blocking the inactivation of sodium ion channels, α-scorpion toxins prolong action potentials.

<i>delta</i>-Palutoxin

delta-Palutoxins (δ-palutoxins) consist of a homologous group of four insect-specific toxins from the venom of the spider Pireneitega luctuosa. They show a high toxicity against Spodoptera litura larvae by inhibiting sodium channels, leading to strong paralytic activity and eventually to the death of the insect.

<span class="mw-page-title-main">Androctonus australis hector insect toxin</span>

Androctonus australis hector insect toxin also known as AaHIT is a scorpion toxin which affects voltage-gated sodium channels. Four different insect toxins, namely AaHIT1, AaHIT2, AaHIT4 and AaHIT5, can be distinguished. It targets insects, except AaHIT4, which is also toxic to crustaceans and mammals.

Hemitoxin (HTX; α-KTx6.15) is a 35-mer basic peptide from the venom of the Iranian scorpion Hemiscorpius lepturus, which reversibly blocks Kv1.1, Kv1.2 and Kv1.3voltage-gated K+ channels.

BotIT2 is a neurotoxin from the scorpion Buthus occitanus tunetanus, which modifies activation and slows down the deactivation of voltage gated sodium channels.

<span class="mw-page-title-main">Cll1</span> Scorpion protein

Toxin Cll1 is a toxin from the venom of the Mexican scorpion Centruroides limpidus limpidus, which changes the activation threshold of sodium channels by binding to neurotoxin binding site 4, resulting in increased excitability.

Centruroides suffusus suffusus toxin II (CssII) is a scorpion β-toxin from the venom of the scorpion Centruroides suffusus suffusus. CssII primarily affects voltage-gated sodium channels by causing a hyperpolarizing shift of voltage dependence, a reduction in peak transient current, and the occurrence of resurgent currents.

LmαTX3 is an α-scorpion toxin from Lychas mucronatus. that inhibits fast inactivation of voltage gated sodium-channels (VGSCs).

LqhIT2 is a long-chain scorpion depressant β-toxin derived from Leiurus quinquestriatus hebraeus. It targets insect voltage-gated sodium channels (Navs) and shifts the voltage dependence of channel activation to a more negative membrane potential.

BmP02, also known as α-KTx 9.1 or Bmkk(6), is a toxin from the Buthus Martensi Karsch (BmK) scorpion. The toxin acts on potassium channels, blocking Kv1.3 and slowing the deactivation of Kv4.2. BmP02 is not toxic to humans or mice.

<span class="mw-page-title-main">Versutoxin</span>

Delta hexatoxin Hv1 is a neurotoxic component found in the venom of the Australian funnel web spider.

Syb-prII-1 is a β-type neurotoxin from the venom of the scorpion Olivierus martensii. It reduces the activity and the expression of the voltage-gated sodium channel Nav1.8.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Mejri, T; Borchani, L; Srairi-Abid, N; Benkhalifa, R; Cestele, S; Regaya, I; Karoui, H; Pelhate, M; Rochat, H; El Ayeb, M (February 2003). "BotIT6: a potent depressant insect toxin from Buthus occitanus tunetanus venom". Toxicon. 41 (2): 163–71. doi:10.1016/S0041-0101(02)00246-5. PMID   12565735.
  2. 1 2 3 4 5 6 7 Bel Haj Rhouma, R; Cérutti-Duonor, M; Benkhadir, K; Goudey-Perrière, F; El Ayeb, M; Lopez-Ferber, M; Karoui, H (December 2005). "Insecticidal effects of Buthus occitanus tunetanus BotIT6 toxin expressed in Escherichia coli and baculovirus/insect cells". Journal of Insect Physiology. 51 (12): 1376–83. doi:10.1016/j.jinsphys.2005.08.008. PMID   16216259.
  3. ↑ Catterall, WA (October 1992). "Cellular and molecular biology of voltage-gated sodium channels". Physiological Reviews. 72 (4 Suppl): S15–48. doi:10.1152/physrev.1992.72.suppl_4.S15. PMID   1332090.
  4. ↑ Schwartz, EF; Mourão, CB; Moreira, KG; Camargos, TS; Mortari, MR (2012). "Arthropod venoms: a vast arsenal of insecticidal neuropeptides". Biopolymers. 98 (4): 385–405. doi:10.1002/bip.22100. PMID   23193602. S2CID   20594739.
  5. ↑ Herrmann, R; Moskowitz, H; Zlotkin, E; Hammock, BD (August 1995). "Positive cooperativity among insecticidal scorpion neurotoxins". Toxicon. 33 (8): 1099–102. doi:10.1016/0041-0101(95)98053-X. PMID   8533143.
  6. ↑ Cestèle, S; Kopeyan, C; Oughideni, R; Mansuelle, P; Granier, C; Rochat, H (15 January 1997). "Biochemical and pharmacological characterization of a depressant insect toxin from the venom of the scorpion Buthacus arenicola". European Journal of Biochemistry. 243 (1–2): 93–9. doi: 10.1111/j.1432-1033.1997.93_1a.x . PMID   9030726.
  7. 1 2 Li, H; Jin, L; Zeng, Z; Wang, M; Zhang, Y; Wang, D (August 1996). "Crystal structure determination of an acidic neurotoxin (BmK M8) from scorpion Buthus martensii Karsch at 0.25 nm resolution". Science in China Series C: Life Sciences. 39 (4): 373–84. CiteSeerX   10.1.1.655.6685 . doi:10.1007/BF02881716. PMID   9388836. S2CID   9569697.
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