title: Investigation of the relationship between the structure and function of Ts2, a neurotoxin from Tityus serrulatus venom.
abstract: 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.
authors.affiliation: Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Camila T
authors.initials: CT
authors.lastname: Cologna
authors.forename: Steve
authors.initials: S
authors.lastname: Peigneur
authors.forename: Joane K
authors.initials: JK
authors.lastname: Rustiguel
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Nonato
authors.forename: Jan
authors.initials: J
authors.lastname: Tytgat
authors.forename: Eliane C
authors.initials: EC
authors.lastname: Arantes
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004594:Electrophysiology; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry* / Q000633:toxicity*; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry* / Q000633:toxicity*; D012605:Scorpions / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000633:toxicity; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014982:Xenopus laevis / Q000378:metabolism
chemical_list: D009498:Neurotoxins; D012604:Scorpion Venoms; D026941:Sodium Channel Blockers; D015222:Sodium Channels