Anuroctoxin (α-KTx 6.12) is a peptide from the venom of the Mexican scorpion ''Anuroctonus phaiodactylus''. This neurotoxin belongs to the alpha family of potassium channel acting peptides. It is a high-affinity blocker of
Kv1.3
Potassium voltage-gated channel, shaker-related subfamily, member 3, also known as KCNA3 or Kv1.3, is a protein that in humans is encoded by the ''KCNA3'' gene.
Potassium channels represent the most complex class of voltage-gated ion channels from ...
channels.
Sources
Anuroctoxin is a
peptide which is derived from the scorpion ''Anuroctonus phaiodactylus''; this scorpion belongs to the scorpion family Iuridae.
Chemistry
Scorpion toxins acting on K+ channels (KTx) are grouped in three different families: the α-,β- and γ-scorpion toxins.
The Anuroctoxin peptide belongs to the α-KTx group,
which are short peptides that block potassium channels, consisting of 30 to 40 amino acids with three or four disulfide bridges.
Based on a
phylogenetic analysis Anuroctoxin is included in subfamily six in the α-KTx
phylogenetic tree
A phylogenetic tree (also phylogeny or evolutionary tree Felsenstein J. (2004). ''Inferring Phylogenies'' Sinauer Associates: Sunderland, MA.) is a branching diagram or a tree showing the evolutionary relationships among various biological spec ...
; its systematic name is α-KTx 6.12.
Structure
Anuroctoxin has 35 amino acids with four disulfide bridges. Its molecular weight is 4082.8 Da.
Target
Patch-clamp
The patch clamp technique is a laboratory technique in electrophysiology used to study ionic currents in individual isolated living cells, tissue sections, or patches of cell membrane. The technique is especially useful in the study of excitab ...
experiments have shown that Anuroctoxin is a potent blocker of
Kv1.3
Potassium voltage-gated channel, shaker-related subfamily, member 3, also known as KCNA3 or Kv1.3, is a protein that in humans is encoded by the ''KCNA3'' gene.
Potassium channels represent the most complex class of voltage-gated ion channels from ...
(
Kd= 0.73 nM) potassium channels.
Besides Kv1.3/KCNA3 channels, Anuroctoxin also significantly inhibits
Kv1.2 (Kd = 6 nM) potassium channels.
Anuroctoxin does not block any of the following channels: calcium-activated KCa3.1/KCNN4 potassium channels, Shaker IR, Kv1.1/KCNA1, and Kv2.1/KCNB1 potassium channels.
Mode of action
The α-KTx inhibition of the potassium channels is mediated by a simple bimolecular plugging mechanism: the extracellular pore, which has a specific receptor site, is occluded by a single toxin molecule binding to it.
Whether this block is voltage dependent, which is common in scorpion toxins
remains to be seen. This pore block is however fully reversible, which implies that it is not a potent neurotoxin.
References
{{Toxins
Ion channel toxins
Neurotoxins
Scorpion toxins