User:StaWy/sandbox

From Wikipedia, the free encyclopedia

Tityustoxin-15 (Ts15 or Potassium channel toxin α-KTx 21.1), which is produced by the Tityus serrulatus (Brazilian scorpion), targets the voltage-gated potassium channels, primarily the subtypes Kv1.2 and Kv1.3. Ts15 is the first member of the new subfamily α-Ktx 21. [1] [2]

Etymology and source[edit]

Etymology[edit]

The full name of the toxin is: Potassium channel toxin α-KTx 21.1. The name refers to its effects on voltage-gated potassium channels (Kv channels) and indicates that it’s the first member of the α-scorpion toxin subfamily 21. [1] [2]

Source[edit]

Ts15 can be isolated from the venom of the Tityus serrulatus, otherwise known as the Brazilian yellow scorpion.[1] This toxin is the most deadly scorpion toxin in Brazil, with a lethality rate of 0.15%. Ts15 is only one of many neurotoxins that can be found in the venom of the Tityus serrulatus.[3]

Chemistry[edit]

Ts15 is a peptide with a sequence length of 36 amino acids, which are crosslinked by three disulfide bridges.[1] The 27th position in the amino acid sequence undergoes N-linked glycosylation.[4] Ts15 is a scorpion short toxin. The rest of the structure of the toxin remains unknown, because its structure is quite unique. Therefore, it cannot easily be compared to other members of the α-family, since the structural similarities between Ts15 and the other α-families are less than 30%.[2]

Target[edit]

Kv channels are the main targets of Ts15. While other members of the α-family generally target both Kv channels and sodium channels (Nav channels), Ts15 only targets Kv channels.[2] Ts15 mainly targets Kv1.2 and Kv1.3: it blocks the channel’s current by 73% and 50% respectively. When all targeted channels are compared, Ts15 has the highest affinity for Kv1.2 channels. Besides these channels, Ts15 also targets Shaker IR channels, Kv1.6 channels [2] and the Kv2.1 channels.[5] The effects of Ts15 are voltage-independent, meaning it can bind to a channel in any state of activation, and they also are reversible. The precise mode of action is currently unknown.

Toxicity and treatment[edit]

Toxicity[edit]

The LD50 of Ts15 is unknown. The symptoms caused solely by Ts15 have not been studied extensively. However, Ts15 is known to block the Kv1.3 channels on autoreactive effector memory T-cells. The binding of the toxin triggers immunosuppression, by decreasing the calcium influx into the cell.[5]

Treatment[edit]

In general, the venom of the Tityus serrulatus is treated with scorpion antivenom serum, named Soro antiscorpionico. A human antibody fragment, serrumab, neutralises most of the venom. However, this antibody works on the entire venomous cocktail of the scorpion.[3] Information about treating Ts15 alone is currently unavailable.

References[edit]

  1. ^ a b c d Martin-Eauclaire, M. F., Pimenta, A. M., Bougis, P. E., & De Lima, M. E. (2016). Potassium channel blockers from the venom of the Brazilian scorpion Tityus serrulatus. Toxicon, 119, 253-265.
  2. ^ a b c d e Cologna, C. T., Peigneur, S., Rosa, J. C., Selistre-de-Araujo, H. S., Varanda, W. A., Tytgat, J., & Arantes, E. C. (2011). Purification and characterization of Ts15, the first member of a new α-KTX subfamily from the venom of the Brazilian scorpion Tityus serrulatus. Toxicon, 58, 54-61.
  3. ^ a b Pucca, M. B., Cerni, F. A., Junior, E. L. P., Bordon, K. D. C. F., Amorim, F. G., Cordeiro, F. A., ... & Arantes, E. C. (2015). Tityus serrulatus venom – A lethal cocktail. Toxicon, 108, 272-284.
  4. ^ http://www.uniprot.org/uniprot/P86270
  5. ^ a b Pucca, M. B., Bertolini, T. B., Cerni, F. A., Bordon, K. C., Peigneur, S., Tytgat, J., ... & Arantes, E. C. (2016). Immunosuppressive evidence of Tityus serrulatus toxins Ts6 and Ts15: insights of a novel K+ channel pattern in T cells. Immunology, 147, 240-250.