Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins

Toxins

Juliana Silva Cassoli¹  Adriano M. C. Pimenta²  Mohitosh Maiti²  Maria Elena de Lima²  Piet Herdewijn³  Caroline M. Cremonez⁴  Etienne Waelkens⁵  Eveline Lescrinier⁵  Jan Tytgat⁵  Eliane C. Arantes⁵  Alexandre A. A. Dutra⁶  Steve Peigneur⁷ 

[1] Pharmacology, University of Leuven (KU Leuven), Campus Gasthuisberg O&Laboratory for Medicinal Chemistry, Rega Institute for Medical Research, University of Leuven (KU Leuven), P.O. Box 922, Leuven 3000, Belgium;Laboratory of Protein Phosphorylation and Proteomics, University of Leuven (KU Leuven), P.O. Box 922, Leuven 3000, Belgium;Laboratório de Toxinas Animais, Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto 14040-903, São Paulo, Brasil;Laboratório de Venenos e Toxinas Animais, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Brasil;N2, P.O. Box 922, Leuven 3000, Belgium;;Toxicology &

关键词: Tityus serrulatus;    scorpion toxin;    Ts11;    neurotoxin;    NMR;    protein structure;    ICK fold;    electrophysiology;    potassium channel;   

DOI  :  10.3390/toxins8100288

来源: DOAJ

【 摘 要 】

To date, several families of peptide toxins specifically interacting with ion channels in scorpion venom have been described. One of these families comprise peptide toxins (called KTxs), known to modulate potassium channels. Thus far, 202 KTxs have been reported, belonging to several subfamilies of KTxs (called α, β, γ, κ, δ, and λ-KTxs). Here we report on a previously described orphan toxin from Tityus serrulatus venom, named Ts11. We carried out an in-depth structure-function analysis combining 3D structure elucidation of Ts11 and electrophysiological characterization of the toxin. The Ts11 structure is highlighted by an Inhibitor Cystine Knot (ICK) type scaffold, completely devoid of the classical secondary structure elements (α-helix and/or β-strand). This has, to the best of our knowledge, never been described before for scorpion toxins and therefore represents a novel, 6th type of structural fold for these scorpion peptides. On the basis of their preferred interaction with voltage-gated K channels, as compared to all the other targets tested, it can be postulated that Ts11 is the first member of a new subfamily, designated as ε-KTx.

【 授权许可】

Unknown