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Investigation of the relationship between the structure and function of Ts2, a neurotoxin from Tityus serrulatus venom
Author(s) -
Cologna Camila T.,
Peigneur Steve,
Rustiguel Joane K.,
ato M. Cristina,
Tytgat Jan,
Arantes Eliane C.
Publication year - 2012
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2012.08545.x
Subject(s) - venom , neurotoxin , scorpion toxin , toxin , sodium channel , cysteine , stereochemistry , rna , scorpion , chemistry , helix (gastropod) , gene isoform , cobra , biology , sodium , biochemistry , gene , enzyme , ecology , organic chemistry , snail , computer science , programming language
Scorpion toxins targeting voltage‐gated sodium (Na V ) channels are peptides that comprise 60–76 amino acid residues cross‐linked by four disulfide bridges. These toxins can be divided in two groups (α and β toxins), according to their binding properties and mode of action. The scorpion α‐toxin Ts2, previously described as a β‐toxin, was purified from the venom of Tityus serrulatus , the most dangerous Brazilian scorpion. In this study, seven mammalian Na V channel isoforms (rNa V 1.2, rNa V 1.3, rNa V 1.4, hNa V 1.5, mNa V 1.6, rNa V 1.7 and rNa V 1.8) and one insect Na V channel isoform (DmNa V 1) were used to investigate the subtype specificity and selectivity of Ts2. The electrophysiology assays showed that Ts2 inhibits rapid inactivation of Na V 1.2, Na V 1.3, Na V 1.5, Na V 1.6 and Na V 1.7, but does not affect Na V 1.4, Na V 1.8 or DmNa V 1. Interestingly, Ts2 significantly shifts the voltage dependence of activation of Na V 1.3 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 β‐strands and one α‐helix, and is arranged in a triangular shape forming a cysteine‐stabilized α‐helix/β‐sheet (CSαβ) motif. Database Model data are available in the PMDB under accession number PM0077533 .