TLTx

Last updated

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. [1]

Contents

Chemistry

3D-structure of TLTx1 (PDB file downloaded from Swiss Model Repository ) TLTx.JPG
3D-structure of TLTx1 (PDB file downloaded from Swiss Model Repository )

TLTx is part of the family of Kv4-specific tarantula toxins, which are short peptides with a disulfide-bonded core domain. Other members of this family are heteropodatoxins and phrixotoxins. [3]

Three homologous peptides (TLTx1, 2 and 3) have been isolated from the venom of the tarantula. They consist of 35 amino acids, with a mass of <5 kDa. [4] They form a total of 3 disulfide bonds between the side chains of cysteine, of which the positions in the sequence are identical in all subtypes of the toxin. The homology with other tarantula toxins suggests that TLTx also forms and inhibitor cystine knot (ICK) motif.

Disulfide bonds between cysteine side chains in the amino acid sequence of TLTx1 TLTx disulfide bonds.JPG
Disulfide bonds between cysteine side chains in the amino acid sequence of TLTx1

Target

The main difference between the three TLTx subtypes is their affinity for the Kv4.2 voltage-dependent potassium channel. TLTx1 has the highest affinity with an IC50 of 193 nM, followed by TLTx2 with an IC50 of about 800 nM. [1] For TLTx3 the IC50 has not been measured.

Mode of action

TLTx1 acts as a gating modifier on Kv4.2 channels. TLTx1 shifts the voltage dependence of activation of Kv4.2 channels to more positive potentials, slows its activation and speeds up its deactivation kinetics. Additionally, TLTx decreases their rate of inactivation. The binding site that TLTx most likely interacts with is the linker region between the transmembrane segments S3 and S4. In addition, the S1-S2 and S5-S6 loops may also play a role. [1]

Toxicity

By blocking the transient Kv4.2 potassium channels, TLTx may interfere with action potential repolarisation, leading to prey paralysis. [5] [ self-published source? ] No fatal episodes have been reported for humans. [6]

Related Research Articles

<span class="mw-page-title-main">Conotoxin</span> Group of neurotoxins

A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus Conus.

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

Heteropodatoxins are peptide toxins from the venom of the giant crab spider Heteropoda venatoria, which block Kv4.2 voltage-gated potassium channels.

Stromatoxin is a spider toxin that blocks certain delayed-rectifier and A-type voltage-gated potassium channels.

<span class="mw-page-title-main">Phrixotoxin</span> Toxin in venom of Phrixotrichus auratus

Phrixotoxins are peptide toxins derived from the venom of the Chilean copper tarantula Phrixotrichus auratus, also named Paraphysa scrofa. Phrixotoxin-1 and -2 block A-type voltage-gated potassium channels; phrixotoxin-3 blocks voltage-gated sodium channels. Similar toxins are found in other species, for instance the Chilean rose tarantula.

AETX refers to a group of polypeptide neurotoxins isolated from the sea anemone Anemonia erythraea that target ion channels, altering their function. Four subtypes have been identified: AETX I, II, III and K, which vary in their structure and target.

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.

<span class="mw-page-title-main">Heteroscodratoxin-1</span>

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.

<span class="mw-page-title-main">Vanillotoxin</span> Chemical compound

Vanillotoxins 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.

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

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.

Huwentoxins (HWTX) are a group of neurotoxic peptides found in the venom of the Chinese bird spider Haplopelma schmidti. The species was formerly known as Haplopelma huwenum, Ornithoctonus huwena and Selenocosmia huwena. While structural similarity can be found among several of these toxins, HWTX as a group possess high functional diversity.

HgeTx1 (systematic name: α-KTx 6.14) is a toxin produced by the Mexican scorpion Hoffmanihadrurus gertschi that is a reversible blocker of the Shaker B K+-channel, a type of voltage-gated potassium channels.

SHTX is a toxin derived from the sea anemone Stichodactyla haddoni; there are four different subtypes, SHTX I, II, III and IV. SHTX I, II and III can paralyze crabs by acting on potassium channels, while SHTX IV works on sodium channels, and is lethal to crabs.

AaTX1 is a scorpion toxin of the α-KTx15 subfamily originally found in the venom of Androctonus australis. The toxin acts as a specific blocker on Kv4.3 voltage-gated potassium channel, thereby abolishing the A-type potassium currents.

APETx1 is a peptide toxin from the venom of the sea anemone Anthopleura elegantissima. The toxin acts as a gating modifier on the human ether-à-go-go-related gene (hERG) channel, a type of voltage-gated potassium channel, and as a blocker of voltage-gated sodium channels, including Nav1.2 and Nav1.8.

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.

Protoxin-II, also known as ProTx-II, PT-II or β/ω-TRTX-Tp2a, is a neurotoxin that inhibits certain voltage-gated calcium and voltage-gated sodium channels. This toxin is a 30-residue disulfide-rich peptide that has unusually high affinity and selectivity toward the human Nav1.7. channel.

<span class="mw-page-title-main">GiTx1</span>

GiTx1 (β/κ-theraphotoxin-Gi1a) is a peptide toxin present in the venom of Grammostola iheringi. It reduces both inward and outward currents by blocking voltage-gated sodium and potassium channels, respectively.

<span class="mw-page-title-main">Ctri9577</span> Scorpion toxin

Ctri9577 (α-KTx15.10) is a neurotoxin present in the venom of the Chaerilus tricostatus scorpion, which is a potent blocker of the voltage-gated potassium channel Kv1.3, and a gating modifier of Kv4.3 channels.

κ-KTx2.5 is a toxin found in the venom of the scorpion, Opisthacanthuscayaporum. The toxin belongs to the κ-KTx family, a channel blocker family that targets voltage-gated potassium channels (Kv) 1.1 and 1.4.

References

  1. 1 2 3 Ebbinghaus, Jan; Legros, Christian; Nolting, Andreas; Guette, Catherine; Celerier, Marie-Louise; Pongs, Olaf; Bähring, Robert (2004). "Modulation of Kv4.2 channels by a peptide isolated from the venom of the giant bird-eating tarantula Theraphosa leblondi". Toxicon. 43 (8): 923–32. Bibcode:2004Txcn...43..923E. doi:10.1016/j.toxicon.2003.12.012. PMID   15208026.
  2. ↑ Kiefer, F.; Arnold, K.; Kunzli, M.; Bordoli, L.; Schwede, T. (2009). "The SWISS-MODEL Repository and associated resources". Nucleic Acids Research. 37 (Database issue): D387–92. doi:10.1093/nar/gkn750. PMC   2686475 . PMID   18931379.
  3. ↑ Rash, Lachlan D.; Hodgson, Wayne C. (2002). "Pharmacology and biochemistry of spider venoms". Toxicon. 40 (3): 225–54. Bibcode:2002Txcn...40..225R. doi:10.1016/S0041-0101(01)00199-4. PMID   11711120.
  4. ↑ Legros, Christian; Célérier, Marie-Louise; Henry, Maud; Guette, Catherine (2004). "Nanospray analysis of the venom of the tarantulaTheraphosa leblondi: A powerful method for direct venom mass fingerprinting and toxin sequencing". Rapid Communications in Mass Spectrometry. 18 (10): 1024–32. Bibcode:2004RCMS...18.1024L. doi:10.1002/rcm.1442. PMID   15150824.
  5. ↑ Schaffner, Brynn (2003). "Goliath Bird Eating Spider".
  6. ↑ Neto, Eraldo (2006). "Bird-spiders (Arachnida, Mygalomorphae) as perceived by the inhabitants of the village of Pedra Branca, Bahia State, Brazil". Journal of Ethnobiology and Ethnomedicine. 2: 50. doi: 10.1186/1746-4269-2-50 . PMC   1654147 . PMID   17101055.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.