title: Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins.
abstract: 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 fromTityus serrulatusvenom, 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.
authors.affiliation: 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. carolmarroni@yahoo.com.br.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Cremonez
authors.affiliation: Laboratory for Medicinal Chemistry, Rega Institute for Medical Research, University of Leuven (KU Leuven), P.O. Box 922, Leuven 3000, Belgium. mohitosh_maiti@yahoo.com.
authors.forename: Mohitosh
authors.initials: M
authors.lastname: Maiti
authors.affiliation: Toxicology & Pharmacology, University of Leuven (KU Leuven), Campus Gasthuisberg O&N2, P.O. Box 922, Leuven 3000, Belgium. steve.peigneur@pharm.kuleuven.be.
authors.forename: Steve
authors.initials: S
authors.lastname: Peigneur
authors.affiliation: 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. jscassoli@gmail.com.
authors.forename: Juliana Silva
authors.initials: JS
authors.lastname: Cassoli
authors.affiliation: 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. aledutra@gmail.com.
authors.forename: Alexandre A A
authors.initials: AA
authors.lastname: Dutra
authors.affiliation: Laboratory of Protein Phosphorylation and Proteomics, University of Leuven (KU Leuven), P.O. Box 922, Leuven 3000, Belgium. etienne.waelkens@med.kuleuven.be.
authors.forename: Etienne
authors.initials: E
authors.lastname: Waelkens
authors.affiliation: Laboratory for Medicinal Chemistry, Rega Institute for Medical Research, University of Leuven (KU Leuven), P.O. Box 922, Leuven 3000, Belgium. eveline.lescrinier@rega.kuleuven.be.
authors.forename: Eveline
authors.initials: E
authors.lastname: Lescrinier
authors.affiliation: Laboratory for Medicinal Chemistry, Rega Institute for Medical Research, University of Leuven (KU Leuven), P.O. Box 922, Leuven 3000, Belgium. piet.herdewijn@rega.kuleuven.be.
authors.forename: Piet
authors.initials: P
authors.lastname: Herdewijn
authors.affiliation: 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. melenalima@icb.ufmg.br.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: de Lima
authors.affiliation: 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. apimenta@icb.ufmg.br.
authors.forename: Adriano M C
authors.initials: AM
authors.lastname: Pimenta
authors.affiliation: 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. ecabraga@fcfrp.usp.br.
authors.forename: Eliane C
authors.initials: EC
authors.lastname: Arantes
authors.affiliation: Toxicology & Pharmacology, University of Leuven (KU Leuven), Campus Gasthuisberg O&N2, P.O. Box 922, Leuven 3000, Belgium. jan.tytgat@pharm.kuleuven.be.
authors.forename: Jan
authors.initials: J
authors.lastname: Tytgat
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D060829:Arthropod Proteins; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D010455:Peptides / Q000737:chemistry* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism / Q000502:physiology; D012604:Scorpion Venoms / Q000737:chemistry*; D014118:Toxins, Biological / Q000737:chemistry* / Q000502:physiology; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D060829:Arthropod Proteins; D010455:Peptides; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; D014118:Toxins, Biological; D061566:Voltage-Gated Sodium Channels
keywords: ICK fold; NMR; Tityus serrulatus; Ts11; electrophysiology; neurotoxin; potassium channel; protein structure; scorpion toxin