ProTx-I

T-type Ca²⁺-Channel Blocker with Na⁺/K⁺-Channel Blocking Activity

ProTx-I was isolated from the venom of the tarantula Thrixopelma pruriens and its primary structure was determined to consist of 35 amino acid residues with three intrachain disulfide bonds[Biochemistry 41, 14734 (2002)]. This peptide shows sequence similarity to hanatoxin1 and belongs to a member of the "inhibitor cystine knot" peptide family.

ProTx-I :
Glu-Cys-Arg-Tyr-Trp-Leu-Gly-Gly-Cys-Ser-
Ala-Gly-Gln-Thr-Cys-Cys-Lys-His-Leu-Val-
Cys-Ser-Arg-Arg-His-Gly-Trp-Cys-Val-Trp-
Asp-Gly-Thr-Phe-Ser

Like other venomous toxins, ProTx-I exerts inhibitory activities for each ion channels; i) T-type Ca²⁺ channel [Cav3.1 (a1G), IC50 = 53 nM], ii) Na⁺ channel [Nav1.2, Nav1.5, Nav1.7 (IC50 = 51 nM), and Nav1.8 (IC50 = 27 nM)], and iii) K⁺ channel [Kv2.1 (IC50 = 411 nM) and Kv1.3 (40% blocking at 730 nM)].

ProTx-I thus elicits multiple channel blocking activities with certain selectivity since K⁺ channel inhibitory activity is relatively weak. ProTx-I is one of the first high-affinity ligands to be identified that possess tetrodotoxin-resistant Na⁺ and T-type Ca²⁺ channel blocking activity. This peptide should prove useful for elucidating the gating mechanism of voltage-dependent ion channels.