New Tricks of an Old Pattern

Abstract

Background: Most scorpion venom peptides adopt a single structural scaffold around four strictly conserved cysteines. Results: Two K ϩ channel-blocking peptides from Tityus venoms share this cysteine spacing but fold into a distinct cystine-

Scorpion venom components that affect ion-channels function

“…Based on primary amino acid sequences and cysteine pairing, KTx have been classified into four families α-, β-, γ- and κ-KTx (Tytgat et al, 1999; Rodríguez de la Vega and Possani, 2004). There are two main types of structural motifs in these peptides: (1) the common motif comprising one or two short α-helices connected to a triple-stranded antiparallel β-sheet stabilized by three or four disulfide bonds, named CSαβ (Rodríguez de la Vega and Posssani, 2004; Mouhat et al, 2004), (2) the α-helix-loop-helix (CSαα) fold consists of two short α-helices connected by a β-turn; only the kappa toxins adopt this fold (Srinivasan et al, 2002; Chagot et al, 2005; Camargos et al, 2011; Saucedo et al, 2012). …”

“…This toxin inhibit the K + current of the Kv1.2 and Kv1.3 channels, showing an IC 50 of 100 and 7 nM, respectively (Saucedo et al, 2012). …”

CHAPTER 7. Scorpion Venoms as a Platform for Drug Development

“…The largest group of described scorpion-venom peptides is constituted by disulde-bridged peptides, 21-77 residues long, with the sequence signature of the cystine stabilized a/b (CSa/b) motif, 15 even if not all of them fold into the most common abb three-dimensional topology. 16 To a large extent the size of CSa/b scorpion venom peptides serves as indication of their mechanism of action: short-chain peptides (smaller than 45 residues) are generally potassium channel blockers and long-chain peptides (55 residues or larger) mostly modulate the activity of sodium channels. 9 Some scorpion CSa/b peptides display a remarkable specicity for certain subtypes of ion channels, and thus great efforts have been made to identify specic modulators of ion channels involved in several channelopathies.…”

Structural Similarity between Defense Peptide from Wheat and Scorpion Neurotoxin Permits Rational Functional Design

“…The most interesting of them in terms of comparison with ␣-hairpinins is the potassium channel blocker -BUTX-Tt2b from the venom of the scorpion Tityus trivittatus (56). It possesses the cysteine motif C 1 X 4 C 2 X 3 C 3 X 8 C 4 X 3 C 5 XC 6 , which in the underlined region resembles plant ␣-hairpinins.…”