Investigation of the relationship between the structure and function of Ts2, a neurotoxin from Tityusserrulatus venom

• Published in: The FEBS journal Vol. 279; no. 8; pp. 1495 - 1504
• Main Authors: Cologna, Camila T, Peigneur, Steve, Rustiguel, Joane K, Nonato, M. Cristina, Tytgat, Jan, Arantes, Eliane C
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01-04-2012
• Subjects: Amino acids; Neurochemistry; Neurotoxicity; Toxins; Venom
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/j.1742-4658.2012.08545.x

Scorpion toxins targeting voltage-gated sodium (NaV) channels are peptides that comprise 60-76 amino acid residues cross-linked by four disulfide bridges. These toxins can be divided in two groups ([alpha] and [beta] toxins), according to their binding properties and mode of action. The scorpion [alpha]-toxin Ts2, previously described as a [beta]-toxin, was purified from the venom of Tityusserrulatus, the most dangerous Brazilian scorpion. In this study, seven mammalian NaV channel isoforms (rNaV1.2, rNaV1.3, rNaV1.4, hNaV1.5, mNaV1.6, rNaV1.7 and rNaV1.8) and one insect NaV channel isoform (DmNaV1) were used to investigate the subtype specificity and selectivity of Ts2. The electrophysiology assays showed that Ts2 inhibits rapid inactivation of NaV1.2, NaV1.3, NaV1.5, NaV1.6 and NaV1.7, but does not affect NaV1.4, NaV1.8 or DmNaV1. Interestingly, Ts2 significantly shifts the voltage dependence of activation of NaV1.3 channels. The 3D structure of this toxin was modeled based on the high sequence identity (72%) shared with Ts1, another T.serrulatus toxin. The overall fold of the Ts2 model consists of three [beta]-strands and one [alpha]-helix, and is arranged in a triangular shape forming a cysteine-stabilized [alpha]-helix/[beta]-sheet (CS[alpha][beta]) motif. Database Model data are available in the PMDB under accession number . [PUBLICATION ABSTRACT]