Ts17, a Tityus serrulatus β-toxin structurally related to α-scorpion toxins

Luis Felipe Santos Menezes; Mariza Mendanha Maranhão; Diogo Vieira Tibery; Adolfo Carlos Barros de Souza; Daniel Oliveira da Mata; Leandro Ambrósio Campos; Amanda Araújo Souza; Sonia Maria de Freitas; Elisabeth Ferroni Schwartz

doi:10.1016/j.bbamem.2022.184057

Ts17, a Tityus serrulatus β-toxin structurally related to α-scorpion toxins

Biochim Biophys Acta Biomembr. 2023 Jan 1;1865(1):184057. doi: 10.1016/j.bbamem.2022.184057. Epub 2022 Oct 12.

Authors

Luis Felipe Santos Menezes¹, Mariza Mendanha Maranhão¹, Diogo Vieira Tibery¹, Adolfo Carlos Barros de Souza¹, Daniel Oliveira da Mata¹, Leandro Ambrósio Campos², Amanda Araújo Souza³, Sonia Maria de Freitas⁴, Elisabeth Ferroni Schwartz⁵

Affiliations

¹ Laboratório de Neurofarmacologia, Departamento de Biologia Celular, Universidade de Brasília, Brasília 70910-900, Distrito Federal, Brazil.
² Laboratório de Neurofarmacologia, Departamento de Biologia Celular, Universidade de Brasília, Brasília 70910-900, Distrito Federal, Brazil; Instituto de Ciências da Saúde, Universidade Paulista, Brasília 70390-130, Distrito Federal, Brazil.
³ Brazilian Biosciences National Laboratory (LNBio), National Center for Research in Energy and Materials (CNPEM), Campinas 13083-970, São Paulo, Brazil.
⁴ Laboratório de Biofísica Molecular, Departamento de Biologia Celular, Universidade de Brasília, Brasília 70910-900, Distrito Federal, Brazil.
⁵ Laboratório de Neurofarmacologia, Departamento de Biologia Celular, Universidade de Brasília, Brasília 70910-900, Distrito Federal, Brazil. Electronic address: efschwa@unb.br.

PMID: 36240866
DOI: 10.1016/j.bbamem.2022.184057

Abstract

Ts17 was purified from the venom of the scorpion Tityus serrulatus, the most dangerous scorpion species in Brazil. The activity on Na_v1.1-Na_v1.7 channels was electrophysiologically characterized by patch-clamp technique. Ts17 amino acid sequence indicated high similarity to alpha-scorpion toxins; however, it presented beta-toxin activity, altering the kinetics of the Na⁺-channels. The most affected subtypes during activation (with and without prepulse) and inactivation phases were Na_v1.2 and Na_v1.5, respectively. For recovery from inactivation, the most affected voltage-gated sodium channel was Na_v1.5. Circular dichroism spectra showed that Ts17 presents mainly β-sheet and unordered structures at all analyzed pHs, and the maximum value of α-helix was found at pH 4.0 (13.3 %). Based on the results, Ts17 might be used as a template to develop a new cardiac drug. Key contribution Purification of Ts17 from Tityus serrulatus, electrophysiological characterization of Ts17 on voltage-gated sodium channel subtypes, β-toxin classification.

Keywords: Beta-toxin; Na(v); Tityus serrulatus; Toxin; Ts17; Voltage-gated sodium channels.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Patch-Clamp Techniques
Scorpion Venoms* / chemistry
Scorpion Venoms* / pharmacology
Scorpions / chemistry
Voltage-Gated Sodium Channels*

Substances

Scorpion Venoms
Voltage-Gated Sodium Channels