Scorpion venom components that affect ion-channels function

Abstract

The number and types of venom components that affect ion-channel function are reviewed. These are the most important venom components responsible for human intoxication, deserving medical attention, often requiring the use of specific anti-venoms. Special emphasis is given to peptides that recognize Na(+)-, K(+)- and Ca(++)-channels of excitable cells. Knowledge generated by direct isolation of peptides from venom and components deduced from cloned genes, whose amino acid sequences are deposited into databanks are nowadays in the order of 1.5 thousands, out of an estimate biodiversity closed to 300,000. Here the diversity of components is briefly reviewed with mention to specific references. Structural characteristic are discussed with examples taken from published work. The principal mechanisms of action of the three different types of peptides are also reviewed. Na(+)-channel specific venom components usually are modifier of the open and closing kinetic mechanisms of the ion-channels, whereas peptides affecting K(+)-channels are normally pore blocking agents. The Ryanodine Ca(++)-channel specific peptides are known for causing sub-conducting stages of the channels conductance and some were shown to be able to internalize penetrating inside the muscle cells.

Keywords: Biodiversity; Functional effect; Ion-channel; Scorpion toxin; Structural features.

Figure 1. Three-dimensional structures of Na-ScTxs

The structures shown are: α-NaScTx AaHII from Androctonus australis Hector (pdb 1SEG), β-NaScTxs Cn2 (pdb 1CN2) and Cn12 (pdb 1PEA) from Centruroides noxius Hoffmann). The structures were obtained from Protein databank (www.pdb.org) and were displayed with PyMOL (www.pymol.org). AaHII is the prototype of α-NaScTxs and Cn2 is a typical β-NaScTx; however, Cn12 is structurally a β-NaScTx, but it has a α-NaScTx effect. All these toxins have a three-dimensional structure highly conserved comprising an α-helix (red) and three or four-stranded anti-parallel β-sheets (blue).

Figure 2. Structures of scorpion toxins affecting K⁺ channels

This figure shows three examples of toxins belonging to: (A) the α-KTx23 subfamily (Vm24; pdb 2K9O), (B) the γ-KTx1 subfamily (ErgTx1; pdb 1PX9) and (C) the α-KTx20 subfamily (Ts16; pdb 2LO7). The latter toxin has a CSαα motif, typical of the κ-KTxs, however, was classified by its primary sequence into of the α-KTx family. The structures were displayed with Pymol (www.pymol.org) and shown in red the α-helix and in blue the β-sheets.

Figure 3. Structure of IpTxa

(A) Schematic diagram of IpTxa, illustrating the location of the β strands (blue), the 3₁₀ helical turn (red), and the disulfide bridges (yellow). (B) Profile of surfaces, negatively charged residues (acid) are shown in red, positively charged residues (basic) are shown in blue, and the residues not charged or hydrophobic are in white (Figure taken from Lee et al., 2004).