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

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...

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Autores principales: Cremonez, Caroline M., Maiti, Mohitosh, Peigneur, Steve, Cassoli, Juliana Silva, Dutra, Alexandre A. A., Waelkens, Etienne, Lescrinier, Eveline, Herdewijn, Piet, de Lima, Maria Elena, Pimenta, Adriano M. C., Arantes, Eliane C., Tytgat, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086648/
https://www.ncbi.nlm.nih.gov/pubmed/27706049
http://dx.doi.org/10.3390/toxins8100288
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author Cremonez, Caroline M.
Maiti, Mohitosh
Peigneur, Steve
Cassoli, Juliana Silva
Dutra, Alexandre A. A.
Waelkens, Etienne
Lescrinier, Eveline
Herdewijn, Piet
de Lima, Maria Elena
Pimenta, Adriano M. C.
Arantes, Eliane C.
Tytgat, Jan
author_facet Cremonez, Caroline M.
Maiti, Mohitosh
Peigneur, Steve
Cassoli, Juliana Silva
Dutra, Alexandre A. A.
Waelkens, Etienne
Lescrinier, Eveline
Herdewijn, Piet
de Lima, Maria Elena
Pimenta, Adriano M. C.
Arantes, Eliane C.
Tytgat, Jan
author_sort Cremonez, Caroline M.
collection PubMed
description 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.
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spelling pubmed-50866482016-11-02 Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins Cremonez, Caroline M. Maiti, Mohitosh Peigneur, Steve Cassoli, Juliana Silva Dutra, Alexandre A. A. Waelkens, Etienne Lescrinier, Eveline Herdewijn, Piet de Lima, Maria Elena Pimenta, Adriano M. C. Arantes, Eliane C. Tytgat, Jan Toxins (Basel) Article 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. MDPI 2016-09-30 /pmc/articles/PMC5086648/ /pubmed/27706049 http://dx.doi.org/10.3390/toxins8100288 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cremonez, Caroline M.
Maiti, Mohitosh
Peigneur, Steve
Cassoli, Juliana Silva
Dutra, Alexandre A. A.
Waelkens, Etienne
Lescrinier, Eveline
Herdewijn, Piet
de Lima, Maria Elena
Pimenta, Adriano M. C.
Arantes, Eliane C.
Tytgat, Jan
Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins
title Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins
title_full Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins
title_fullStr Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins
title_full_unstemmed Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins
title_short Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins
title_sort structural and functional elucidation of peptide ts11 shows evidence of a novel subfamily of scorpion venom toxins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086648/
https://www.ncbi.nlm.nih.gov/pubmed/27706049
http://dx.doi.org/10.3390/toxins8100288
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