Use of Venom Peptides to Probe Ion Channel Structure and Function

Abstract

Venoms of snakes, scorpions, spiders, insects, sea anemones, and cone snails are complex mixtures of mostly peptides and small proteins that have evolved for prey capture and/or defense. These deadly animals have long fascinated scientists and the public. Early studies isolated lethal components in the search for cures and understanding of their mechanisms of action. Ion channels have emerged as targets for many venom peptides, providing researchers highly selective and potent molecular probes that have proved invaluable in unraveling ion channel structure and function. This minireview highlights molecular details of their toxin-receptor interactions and opportunities for development of peptide therapeutics.

New Tricks of an Old Pattern

“…Venoms contain, among others components, peptide toxins capable of interacting specifically with potassium, sodium, and calcium channels (3)(4)(5). These toxic peptides have contributed considerably to the understanding of the structure and functional mechanism of the ion channels (6). Some of them are considered good candidates for the design and development of new drugs (7), although the number of structural and functional analyses of these peptides is still limited (8).…”

“…Potassium channels blocker toxins (KTx) 6 can be classified into four subfamilies accordingly to the accepted nomenclature: ␣, ␤, ␥, and (9, 10). ␣-KTx are peptides of 23-43 amino acids stabilized by three to four disulfide bonds, two of which are strictly conserved and link an ␣-helix and one strand of a ␤-sheet within the so-called cystine-stabilized ␣/␤ scaffold (CS␣/␤), the most common among scorpion toxins (10,11).…”

A Case Report: İsolated Troponin I Elevation After Scorpion Sting

“…Otonomik aktivitenin daha çok sempatik dalı aktiftir. 5,6 Klinik olarak ağrı, uyuşma, kaşıntı, hiperemi, priapizm gibi lokal bulguların yanında solunum zorluğu, akciğer ödemi, akut respiratuvar distres sendromu, hipersalivasyon, taşikardi, hipertansiyon, miyokard disfonksiyonu, aritmi, nöbet, ensefolapati, afazi, dissemine intravaküler koagülasyon, intraserebral kanama, hiperglisemi ve istemsiz ekstremite hareketleri gibi sistemik bulgular da görülebilir. 7 Semptomlar genelde ilk 5 dk-4 saat arasında başlar, çocuklarda ve baş boyun bölgesinden olan zehirlenmelerde klinik süreç daha ağır seyreder.…”

Subtype-Selective Activation of Kv7 Channels by AaTXKβ(2–64), a Novel Toxin Variant from theAndroctonus australisScorpion Venom

“…The ability of AaTXKb to cause an hyperpolarization shift in K v 7.4 channels gating is reminiscent of the effects exerted on voltage-gated Na 1 channels by b-scorpion toxins acting at site 4 (Dutertre and Lewis, 2010); these toxins enhance voltage-dependent activation of Na 1 channels by modifying the movement of the S 4 segments via a voltagesensor trapping mechanism (Catterall et al, 2007). Toxininduced sensor-trapping can also occur in voltage-gated Ca 21 channels (agatoxins from spiders) (McDonough, 2007), and in voltage-gated K 1 channels of the K v 2 and K v 4 (hanatoxins from tarantula) (Swartz and MacKinnon, 1997) or K v 3 and K v 11 (sea anemone toxins) (Diochot and Lazdunski, 2009) subclasses.…”