AETX refers to a group of polypeptide

neurotoxins Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature nerv ...

isolated from the

sea anemone Sea anemones are a group of predation, predatory marine invertebrates of the order (biology), order Actiniaria. Because of their colourful appearance, they are named after the ''Anemone'', a terrestrial flowering plant. Sea anemones are classifi ...

''Anemonia erythraea'' that target

ion channels Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...

, altering their function. Four subtypes have been identified: AETX I, II, III and K, which vary in their structure and target.

Etymology and Source

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

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. As reported by Norton ''et al.'', 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.

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. 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. 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 ''Phoneutria nigriventer'' is a species of Medically significant spider bites, medically significant spider in the family Ctenidae, found in the Southern Cone of South America (Brazil, Uruguay, Paraguay, and Argentina). Along with other members o ...

'', an aggressive Brazilian spider. These similarities concern the position of 7 half-

cystine Cystine is the oxidized derivative of the amino acid cysteine and has the formula (SCH2CH(NH2)CO2H)2. It is a white solid that is poorly soluble in water. As a residue in proteins, cystine serves two functions: a site of redox reactions and a me ...

(oxidized cysteine) residues in both AETX II and III, consistent with the conserved half-cystine residues throughout the ''P. nigriventer'' neurotoxins. 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.

AETX K

AETX K is a member of the Type I potassium channel toxin family. 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.

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 Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...

, slowing down their inactivation. 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. 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 Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cel ...

Toxicity

The 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. The LD50 of AETX K is not known so far, but its 50% inhibitory concentration (

IC50 The half maximal inhibitory concentration (IC50) is a measure of the potency of a substance in inhibiting a specific biological or biochemical function. IC50 is a quantitative measure that indicates how much of a particular inhibitory substance ...

) was determined as 91 nM.

References

External links

Protein details:
AETX IAETX IIAETX IIIAETX K
Neurotoxins Ion channel toxins Sea anemone toxins