Birtoxin

Birtoxin
Category	Ion channel toxin, Neurotoxin
Species	Parabuthus transvaalicus[1]
Target	voltage-gated sodium channel [1]
Symptoms	Lethal, tachypnea, convulsions, tremors
Taxonomic ID	170972 [1]
Sequence length	58 AA [1]

Birtoxin is a neurotoxin from the venom of the South African Spitting scorpion (Parabuthus transvaalicus). By changing sodium channel activation, the toxin promotes spontaneous and repetitive firing.

Sources

South African spitting scorpion (Parabuthus transvaalicus)

Birtoxin was isolated from the venom of the South African Spitting scorpion.^[1] It is a peptide that is moderately toxic but very abundant in the venom.^[1] Other peptide toxins found in the venom include: dortoxin, a lethal peptide; bestoxin, which causes writhing in mice; and altitoxin, a highly depressant peptide.^[2]

Chemistry

Generally, peptide neurotoxins can be divided into two major families, the ‘long chain neurotoxins’ (LCN) with 60- to 70-residue range and known to contain eight cysteine residues; and the ‘short chain neurotoxins’ (SCN) with 30 to 40 peptides with six or eight cysteine residues. Birtoxin, together with other birtoxin-like peptides including bestoxin, is 58 amino-acid residues long, close to the ‘long chain’ family but with six cysteine residues. Birtoxin is reticulated by three disulfide bridges, instead of four, compared to other LCNs .^[3] Therefore it is considered to be the evolutionary link between ‘long chain’- and ‘short chain’- families.^[4][5][6][7]

Mode of action

Birtoxin affects the gating mechanism of sodium channels by binding to neurotoxin receptor site 4 of the channel, resulting in the lowering of the voltage threshold of the channel and a reduction in the current amplitude. Due to the change in the activation the sodium channel will open at smaller depolarisations. This causes increased excitability, which leads to symptoms such as convulsions, continuous urination, tremors and tachypnea (faster breathing).^[1][8]

Toxicity

Birtoxin only affects mammals. No effect is found on reptiles, insects or fish. In experiments performed on mice, symptoms such as convulsions, continuous urination, tremors and tachypnea occurred 10 minutes after injection and increased during 30 minutes. An injection of 1 μg of birtoxin resulted in severe neurotoxic effects for 24 hours, but this dose is not lethal to mice. LD₉₉ in mice is achieved at 2 μg.^[1]

An antibody against the N-terminus of the birtoxin protein structure has been shown to neutralize the venom of the South African spitting scorpion, and such antibodies may be useful clinically to treat envenomation.^[9]

References

1. Inceoglu, B.; Lango, J.; Wu, J.; Hawkins, P.; Southern, J.; Hammock, B.D. (2001). "Isolation and characterization of a novel type of neurotoxic peptide from the venom of the South African scorpion Parabuthus transvaalicus (Buthidae)". European Journal of Biochemistry 268: 5407–5413. doi:10.1046/j.0014-2956.2001.02479.x. PMID 11606203.
2. Inceoglu, B; J Lango; I Pessah; B Hammock (2005). "Three structurally related, highly potent, peptides from the venom of possess divergent biological activity". Toxicon 45 (6): 727–733. doi:10.1016/j.toxicon.2005.01.020. ISSN 0041-0101. PMID 15804521.
3. Martin-Eauclaire, M-F; Cearda, B.; Bosmans, F.; Rossoa, J-P.; Tytgat, J.; Bougisa, P.E. (1999). "New "Birtoxin analogs" from Androctonus australis venom". Biochemical and Biophysical Research Communications 333 (2): 524–530. doi:10.1016/j.bbrc.2005.05.148. PMID 15963953.
4. Possani, L.D.; Becerrill, B.; Delepierre, M.; Tytgat Hammock, J. (1999). "Scorpion toxins specific for Na+-channels". European Journal of Biochemistry 264: 287–300. doi:10.1046/j.1432-1327.1999.00625.x. PMID 10491073.
5. Lebreton, F.; Delepierre, M.; Ramirez, A.N.; Balderas, C.; Possani, L.D. (1994). "Primary and NMR three-dimensional structure determination of a novel crustacean toxin from the venom of the scorpion Centruroides limpidus limpidus Karsch". Biochemistry. 33(37): 11135–11149. doi:10.1021/bi00203a010. PMID 7727365.
6. Lebreton, F.; Delepierre, M.; Ramirez, A.N.; Balderas, C.; Possani, L.D. (1994). "Purification and primary structure of low molecular mass peptides from scorpion (Buthus sindicus) venom". Comparative Biochemistry and Physiology – Part A: Molecular & Integrative Physiology 121 (4): 323–332. doi:10.1016/S1095-6433(98)10140-X.
7. Gordon, D.; Savarin, P.; Gurevitz, M.; Zinn-Justin, S. (1998). "Functional anatomy of scorpion toxins affecting sodium channels". Toxin Reviews 17: 131–159. doi:10.3109/15569549809009247.
8. Cestèle, S.; Catterall, W.A. (2000). "Molecular mechanisms of neurotoxin action on voltage-gated sodium channels". Biochimie 82 (9–10): 883–892. doi:10.1016/S0300-9084(00)01174-3. PMID 11086218.
9. Inceoglu, B; J Lango; A Rabinovich; P Whetstone; B Hammock (2006). "The neutralizing effect of a polyclonal antibody raised against the N-terminal eighteen-aminoacid residues of birtoxin towards the whole venom of Parabuthus transvaalicus". Toxicon 47 (2): 144–149. doi:10.1016/j.toxicon.2005.08.018. ISSN 0041-0101. PMID 16356521.