Abstract
The Colombian scorpion Centruroides margaritatus produces a venom considered of low toxicity. Nevertheless, there are known cases of envenomation resulting in cardiovascular disorders, probably due to venom components that target ion channels. Among them, the human ether-à-go-go-Related gene (hERG1) potassium channels are critical for cardiac action potential repolarization and alteration in its functionality are associated with cardiac disorders. This work describes the purification and electrophysiological characterization of a Centruroides margaritatus venom component acting on hERG1 channels, the CmERG1 toxin. This novel peptide is composed of 42 amino acids with a MW of 4792.88 Da, folded by four disulfide bonds and it is classified as member number 10 of the γ-KTx1 toxin family. CmERG1 inhibits hERG1 currents with an IC50 of 3.4 ± 0.2 nM. Despite its 90.5% identity with toxin ɣ-KTx1.1, isolated from Centruroides noxius, CmERG1 completely blocks hERG1 current, suggesting a more stable plug of the hERG channel, compared to that formed by other ɣ-KTx.
Highlights
Scorpions are arachnids of wide geographic distribution, with around 2200 species described in families recognized worldwide [1]
Peptides that act as ion channel modulators are the main agents responsible for the venom toxicity and they have been classified according to their targets into: sodium scorpion toxins (NaScTx), with molecular masses between 6–8 kDa [6], potassium scorpion toxins (KScTx), with molecular masses between 3–5 kDa [7,8], and calcium scorpion toxins (CaScTx) that comprise peptides acting on voltage gated calcium channels and that modulate ryanodine receptors [9,10]
We describe the characterization of C. margaritatus venom in order to determine its activity on voltage-gated sodium and potassium channels
Summary
Scorpions are arachnids of wide geographic distribution, with around 2200 species described in families recognized worldwide [1]. Many details of the toxin-channel interaction have been clarified and models of different mechanisms of toxin binding have been described [11,12,13]. Based on their structural and functional characteristics, KScTx have been classified into seven subfamilies: α-Ktx, β-Ktx, G-KTx, δ-KTx, ε-Ktx, κ-KTx, and L-KTx (kalium database) [14]. The G-KTx family comprises toxins that selectively bind to ERG (Ether-à-go-go-Related Gene) potassium channels. These channels are expressed in many tissues and they are especially important for the repolarization of the cardiac action potential. Mutations in the erg gene are responsible for congenital long
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