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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Cologna, Camila T. [1] ; Peigneur, Steve [2] ; Rustiguel, Joane K. [1] ; Nonato, M. Cristina [1] ; Tytgat, Jan [2] ; Arantes, Eliane C. [1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Fis & Quim, BR-14040903 Ribeirao Preto - Brazil
[2] Katholieke Univ Leuven, Toxicol Lab, Louvain - Belgium
Total Affiliations: 2
Document type: Journal article
Source: FEBS Journal; v. 279, n. 8, p. 1495-1504, APR 2012.
Web of Science Citations: 25
Abstract

Scorpion toxins targeting voltage-gated sodium (NaV) channels are peptides that comprise 6076 amino acid residues cross-linked by four disulfide bridges. These toxins can be divided in two groups (a and beta toxins), according to their binding properties and mode of action. The scorpion a-toxin Ts2, previously described as a beta-toxin, was purified from the venom of Tityus serrulatus, 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 a-helix, and is arranged in a triangular shape forming a cysteine-stabilized a-helix/beta-sheet (CSa beta) motif. (AU)

FAPESP's process: 05/54855-0 - Animal toxins: structure, function and biotechnological applications
Grantee:Suely Vilela
Support type: Research Projects - Thematic Grants