AETX

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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.

Contents

Etymology and Source

The four subtypes of AETX (Anemonia erythraea toxins) are produced by the sea anemone Anemonia erythraea. [1]

Chemistry

AETX I

AETX I consists of 47 amino acids. The determined molecular mass appears to be approximately 5 kDa. It is classified into Type I voltage-gated sodium channel neurotoxins. [1] As reported by Norton et al., [2] this group consists of polypeptide neurotoxins with an average of 46-49 amino acids and 27 residues that are highly conserved. AETX I shares 21 of the 27 conserved residues with the representatives of Type I polypeptide toxins from sea anemone. [1]

AETX II & III

AETX II and AETX III have not yet been categorized since their structure does not correspond to any known polypeptide neurotoxins from sea anemone. [1] AETX II is composed of 59 amino acid residues and has a molecular mass of 6506 Da. AETX III has the same number of amino acid residues and a molecular mass of 6558 Da. [1] AETX II and III are highly homologous with a similarity percentage of 94.9%.

Both AETX II and III show sequence similarities to the neurotoxin TxI isolated from Phoneutria nigriventer , an aggressive Brazilian spider. These similarities concern the position of 7 half-cystine (oxidized cysteine) residues in both AETX II and III, consistent with the conserved half-cystine residues throughout the P. nigriventer neurotoxins. [1] The amino acid sequence of AETX I differs from the amino acid sequences of AETX II and III. AETX I is rich in the amino acids asparagine and aspartic acid and has no lysine while AETX II and III both have a high number of half-cystines. All three polypeptides have in common that glycine is the most abundant amino acid. [1]

AETX K

AETX K is a member of the Type I potassium channel toxin family. [3] However, in contrast to the other members of this family which have 35-37 amino acid residues, AETX K consists of 83 amino acid residues; it has a molecular mass of 3999.3 Da. It shares six conserved Cys residues with the other members of Type I potassium channel toxins. [3]

Target and Mode of action

AETX I is part of the sea anemone sodium channel inhibitory subfamily 1 and binds to the neurotoxin receptor site 3 of voltage-gated sodium channels, slowing down their inactivation. [4] The mode of action of AETX II and III is not known, but they show structural similarity to spider toxins and therefore may act the same way, i.e. they might activate voltage dependent sodium channels. [1] AETX K belongs to the group of type 1 sea anemone potassium channel toxins. Its lysine-tyrosine pair (21Lys and 22Tyr) seems to be crucial for its binding to potassium channels. [3]

Toxicity

The LD50 against crabs was estimated for AETX I (2.2 µg/kg), II (0.53 µg/kg) and III (0.28 µg/kg). None of these toxins shows a strong toxic effect in mice. [1] The LD50 of AETX K is not known so far, but its 50% inhibitory concentration (IC50) was determined as 91 nM. [3]

Related Research Articles

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<span class="mw-page-title-main">Sea anemone neurotoxin</span>

Sea anemone neurotoxin is the name given to neurotoxins produced by sea anemones with related structure and function. Sea anemone neurotoxins can be divided in two functional groups that either specifically target the sodium channel or the potassium channel.

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.

Hainantoxins (HNTX) are neurotoxins from the venom of the Chinese bird spider Haplopelma hainanum. Hainantoxins specifically inhibit tetrodotoxin-sensitive Voltage-gated sodium channels, thereby causing blockage of neuromuscular transmission and paralysis. Currently, 13 different hainantoxins are known, but only HNTX-I, -II, -III, -IV and -V have been investigated in detail.

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Halcurin is a polypeptide neurotoxin from the sea anemone Halcurias sp. Based on sequence homology to type 1 and type 2 sea anemone toxins it is thought to delay channel inactivation by binding to the extracellular site 3 on the voltage gated sodium channels in a membrane potential-dependent manner.

Calitoxin, also known as CLX, is a sea anemone neurotoxin produced by the sea anemone Calliactis parasitica. It targets crabs and octopuses, among other invertebrates. Two isoforms have been identified, both of which are formed from precursors stored in the stinging cells of the anemone. Once the toxin is activated and released, it causes paralysis by increasing neurotransmitter release at invertebrate neuromuscular junctions. Along with several other toxins derived from anemones, CLX is useful in ion channel research. Certain structural aspects of calitoxin are dissimilar from sea anemone toxins that also target the sodium ion channels. Other toxins resembling calitoxin function in completely different ways.

Cangitoxin, also known as CGTX or CGX, is a toxin purified from the venom of the sea anemone Bunodosoma cangicum, which most likely acts by prolonging the inactivation of voltage-gated sodium channels.

BgK is a neurotoxin found within secretions of the sea anemone Bunodosomagranulifera which blocks voltage-gated potassium channels, thus inhibiting neuronal repolarization.

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Kaliseptine (AsKS) is a neurotoxin which can be found in the snakelocks anemone Anemonia viridis. It belongs to a class of sea anemone neurotoxins that inhibits voltage-gated potassium channels.

Blood-depressing substance-1 (BDS-1), also known as kappa-actitoxin-Avd4a, is a polypeptide found in the venom of the snakelocks anemone Anemonia sulcata. BDS-1 is a neurotoxin that modulates voltage-dependent potassium channels, in particular Kv3-family channels, as well as certain sodium channels. This polypeptide belongs to the sea anemone type 3 toxin peptide family.

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.

Kalicludine (AsKC) is a blocker of the voltage-dependent potassium channel Kv1.2 found in the snakeslocks anemone Anemonia viridis, which it uses to paralyse prey.

BcIII

BcIII is a polypeptide sea anemone neurotoxin isolated from Bunodosoma caissarum. It targets the site 3 of voltage-gated sodium channels, thus mainly prolonging the inactivation time course of the channel.

ATX-II, also known as neurotoxin 2, Av2, Anemonia viridis toxin 2 or δ-AITX-Avd1c, is a neurotoxin derived from the venom of the sea anemone Anemonia sulcata. ATX-II slows down the inactivation of different voltage-gated sodium channels, including Nav1.1 and Nav1.2, thus prolonging action potentials.

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

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<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.

AsKC11 is a toxin found in the venom of the sea anemone, Anemonia sulcata. This toxin is part of the Kunitz peptide family and has been shown to be an activator of G protein-coupled inwardly-rectifying potassium (GIRK) channels 1/2, involved in the regulation of cellular excitability. 

References

  1. 1 2 3 4 5 6 7 8 9 Shiomi, Kazuo; Qian, Wen-Hong; Lin, Xin-Yu; Shimakura, Kuniyoshi; Nagashima, Yuji; Ishida, Masami (1997). "Novel polypeptide toxins with crab lethality from the sea anemone Anemonia erythraea". Biochimica et Biophysica Acta (BBA) - General Subjects. 1335 (1–2): 191–8. doi:10.1016/S0304-4165(96)00137-7. PMID   9133656.
  2. ↑ Norton, Raymond S. (1991). "Structure and structure-function relationships of sea anemone proteins that interact with the sodium channel". Toxicon. 29 (9): 1051–84. doi:10.1016/0041-0101(91)90205-6. PMID   1686683.
  3. 1 2 3 4 Hasegawa, Yuichi; Honma, Tomohiro; Nagai, Hiroshi; Ishida, Masami; Nagashima, Yuji; Shiomi, Kazuo (2006). "Isolation and cDNA cloning of a potassium channel peptide toxin from the sea anemone Anemonia erythraea". Toxicon. 48 (5): 536–42. doi:10.1016/j.toxicon.2006.07.002. PMID   16905168.
  4. ↑ Catterall, William A.; Cestèle, Sandrine; Yarov-Yarovoy, Vladimir; Yu, Frank H.; Konoki, Keiichi; Scheuer, Todd (2007). "Voltage-gated ion channels and gating modifier toxins". Toxicon. 49 (2): 124–41. doi:10.1016/j.toxicon.2006.09.022. PMID   17239913.

Further reading

Protein details:

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