Hg1, Novel Peptide Inhibitor Specific for Kv1.3 Channels from First Scorpion Kunitz-type Potassium Channel Toxin Family

Abstract

Background:The potassium channel inhibitory activity of scorpion Kunitz-type toxins has not yet been determined. Results: We identified the first scorpion Kunitz-type potassium channel toxin family with three groups and seven members. Conclusion: A novel peptide, Hg1, specific for Kv1.3 channel, was found. Significance: Kunitz-type toxins are a new source to screen and design potential peptides for diagnosing and treating Kv1.3-mediated autoimmune diseases.

Unique diversity of the venom peptides from the scorpion Androctonus bicolor revealed by transcriptomic and proteomic analysis

“…Until now, a total of seven Kunitz-type toxins have been identified from different species of scorpions, including BmKTT-1, BmKTT-2 and BmKTT-3 from M. martensii Karsch, Hg1 from Hadrurus gertschi, and LmKTT-1a, LmKTT-1b and LmKTT-1c from L. mucronatus [65][66][67]. These toxins can be classified into two groups: toxins with three disulfide bridges, and those with four disulfide bridges [66].…”

Selective Inhibition of CCR7− Effector Memory T Cell Activation by a Novel Peptide Targeting Kv1.3 Channel in a Rat Experimental Autoimmune Encephalomyelitis Model

“…were synthesized to target the Kv1.3 channel as a new therapy for MS. However, novel peptides remain required for sufficient specificity to distinguish between Kv1.3 and other related Kv1.x channels (16,17). Moreover, although Kv1.3 blocker peptides, such as ShK (a 35-AA polypeptide isolated from the sea anemone Stichodactyla helianthus), efficiently attenuate the severity of experimental autoimmune encephalomyelitis (EAE), a model for MS (18,19), the mechanisms underlying the peptidemediated inhibition of activation and proliferation of primary T EM cells derived from the EAE model are poorly understood.…”

Variability of Potassium Channel Blockers in Mesobuthus eupeus Scorpion Venom with Focus on Kv1.1

“…Importantly, some of the toxins display remarkable selectivity with respect to different potassium channel isoforms (11)(12)(13)(14)(15), a property that justifies their potential as drug leads (16). Alternatively, high selectivity may be achieved by means of chemical modification and targeted or random mutagenesis of natural peptide molecules (17)(18)(19)(20).…”

“…Potassium channel pore blockers from scorpions described thus far are known to belong to at least five types of fold as follows: (i) cysteine-stabilized ␣/␤ motif (CS␣/␤) (22); (ii) inhibitor cystine knot (ICK) (23); (iii) Kunitz bovine pancreatic trypsin inhibitortype fold (14); (iv) ␣-helical hairpin with two disulfide bridges (CS␣/␣ 2(S-S)) (24); and (v) ␣-helical hairpin with three disulfide bridges (CS␣/␣ 3(S-S)) (25). The most populated class is CS␣/␤, in turn consisting of the following three families: ␣-, ␤-, and ␥-KTx (26).…”