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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
Cologna, Camila T. [1] ; Peigneur, Steve [2] ; Rustiguel, Joane K. [1] ; Nonato, M. Cristina [1] ; Tytgat, Jan [2] ; Arantes, Eliane C. [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: FEBS Journal; v. 279, n. 8, p. 1495-1504, APR 2012.
Citações Web of Science: 25
Resumo

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)

Processo FAPESP: 05/54855-0 - Toxinas animais: estrutura, função e aplicações biotecnológicas
Beneficiário:Suely Vilela
Linha de fomento: Auxílio à Pesquisa - Temático