Vanillotoxin

Last updated
Vanillotoxin-1
VaTx1.JPG
Names
Other names
Tau-theraphotoxin-Pc1a, VaTx1
Identifiers
ChemSpider
  • none
Properties
Molar mass 4008.5 g/mol [1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Vanillotoxins (VaTxs, subtypes VaTx1, VaTx2, and VaTx3) are neurotoxins found in the venom of the tarantula Psalmopoeus cambridgei . They act as agonists for the transient receptor potential cation channel subfamily V member 1 (TRPV1), activating the pain sensory system. VaTx1 and 2 also act as antagonists for the Kv2-type voltage-gated potassium channel (Kv2), inducing paralytic behavior in small animals. [1]

Contents

Origin

P. cambridgei, a tarantula from Trinidad, uses its venom to paralyze its prey. Amongst other compounds, this venom contains all three subtypes of VaTxs: VaTx1, VaTx2, and VaTx3. [1] The name of the toxin was derived from the vanilloid receptor TRPV1, to which the VaTxs bind.

Chemistry

Vanillotoxins have close homology to other inhibitor cystine knot (ICK) toxins. [1] ICK toxins are best known as blockers of cation channels. [2] The exact structure of the VaTxs has not yet been deduced, although some preliminary models have been proposed. VaTxs are 53-82% identical in amino acid sequence. [3] VaTx1 and VaTx2 have an almost identical structure, while VaTx3 shows some diversity in its extruding protein loop.

Targets

All three subtypes of VaTxs act as agonists for TRPV1. [1] EC50 of VaTx1, VaTx2, and VaTx3 for heterologously expressed TRPV1 channels is around 12, 2.5 and 0.3 μM, respectively. [1] VaTx1 and VaTx2 also bind to the Kv2 channel, although VaTx2 with a lower affinity than VaTx1. VaTx2 becomes effective on Kv2 at a minimal concentration of 40 μM.

Mode of action

In humans, the effect of VaTxs has not been systematically studied. In general, the venom of P. cambridgei is known to produce pain, but the amount of toxin that is present in a bite is too low to cause serious health problems [1] . The effects of VaTxs on TRPV1 and Kv2 have been studied by injecting VaTxs subcutaneously in mice. [1] VaTxs bind to the extracellular pore domain of TRPV1 in the peripheral nervous system [3] causing the opening of the pore and cation influx, therefore triggering the activation of the pain system. Despite the similar architecture of TRPV1 and Kv2, VaTx1 and VaTx2 bind to the voltage-sensing domain of Kv2 rather than the pore-domain. [3] By doing so, they increase the action potential threshold in the neuromuscular junction, eliciting paralytic behavior.

Related Research Articles

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Phrixotoxin

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Jingzhaotoxin proteins are part of a venom secreted by Chilobrachys jingzhao, the Chinese tarantula. and act as neurotoxins. There are several subtypes of jingzhaotoxin, which differ in terms of channel selectivity and modification characteristics. All subspecies act as gating modifiers of sodium channels and/or, to a lesser extent, potassium channels.

Heteroscodratoxin-1

Heteroscodratoxin-1 is a neurotoxin produced by the venom glands of Heteroscodra maculata that shifts the activation threshold of voltage-gated potassium channels and the inactivation of Nav1.1 sodium channels to more positive potentials.

<i>delta</i>-Palutoxin

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Guangxitoxin

Guangxitoxin, also known as GxTX, is a peptide toxin found in the venom of the tarantula Plesiophrictus guangxiensis. It primarily inhibits outward voltage-gated Kv2.1 potassium channel currents, which are prominently expressed in pancreatic β-cells, thus increasing insulin secretion.

Hanatoxin is a toxin found in the venom of the Grammostola spatulata tarantula. The toxin is mostly known for inhibiting the activation of voltage-gated potassium channels, most specifically Kv4.2 and Kv2.1, by raising its activation threshold.

Theraphosa leblondi toxin (TLTx) is a toxin occurring in three different forms (subtypes) that are purified and sequenced from the venom of the giant tarantula Theraphosa blondi. This toxin selectively inhibits Kv4.2 voltage-gated potassium channels by acting as a gating modifier.

Mambalgins

Mambalgins are peptides found in the venom of the black mamba, an elapid snake. Mambalgins are members of the three-finger toxin (3FTx) protein family and have the characteristic three-finger protein fold. First reported by French researchers in 2012, mambalgins are unusual members of the 3FTx family in that they have the in vivo effect of causing analgesia without apparent toxicity. Their mechanism of action is potent inhibition of acid-sensing ion channels.

Butantoxin (BuTX) is a compound of the venom of three Brazilian and an Argentinean scorpion species of the genus Tityus. Butantoxin reversibly blocks the voltage-gated K+ channels Shaker B and Kv1.2, and the Ca2+-activated K+ channelsKCa 1.1 and KCa 3.1.

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RhTx is a small peptide toxin from Scolopendra subspinipes mutilans, also called the Chinese red-headed centipede. RhTx binds to the outer pore region of the temperature regulated TRPV1 ion channel, preferably in activated state, causing a downwards shift in the activation threshold temperature, which leads to the immediate onset of heat pain.

GTx1-15 is a toxin from the Chilean tarantula venom that acts as both a voltage-gated calcium channel blocker and a voltage-gated sodium channel blocker.

ImKTx88

ImKTx88 is a selective inhibitor of the Kv1 ion channel family that can be isolated from the venom of the Isometrus maculatus. This peptide belongs to the α-KTx subfamily and is classified as a pore-blocking toxin.

LmαTX5 is an α-scorpion toxin which inhibits the fast inactivation of voltage-gated sodium channels. It has been identified through transcriptome analysis of the venom gland of Lychas mucronatus, also known as the Chinese swimming scorpion – a scorpion species which is widely distributed in Southeast Asia.

Protoxin-1, or Beta/omega-theraphotoxin-Tp1a, is a 35-amino-acid peptide neurotoxin extracted from the venom of the tarantula Thrixopelma pruriens. Protoxin-1 belongs to the inhibitory cystine knot (ICK) family of peptide toxins, which have been known to potently inhibit voltage-gated ion channels. Protoxin-1 selectively blocks low voltage threshold “T-type” calcium channels., voltage gated sodium channels and the nociceptor cation channel TRPA1. Due to its unique ability to bind to TRPA1, Protoxin-1 has been implicated as a valuable pharmacological reagent with potential applications in clinical contexts with regards to pain and inflammation

References

  1. 1 2 3 4 5 6 7 8 Siemens J (2006). "Ion Spider toxins activate the capsaicin receptor to produce inflammatory pain". Nature. 444 (7116): 208–212. Bibcode:2006Natur.444..208S. doi:10.1038/nature05285. PMID   17093448. S2CID   4387600.
  2. ↑ Cromer B, McIntyre P (2007). "Painful toxins acting at TRPV1". Toxicon. 51 (2): 163–173. doi:10.1016/j.toxicon.2007.10.012. PMID   18061640.
  3. 1 2 3 Bohlen CJ, Julius D (2012). "Receptor-targeting mechanisms of pain-causing toxins: How ow?". Toxicon. 60 (3): 254–264. doi:10.1016/j.toxicon.2012.04.336. PMC   3383939 . PMID   22538196.
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