Isolation and characterization of Ts19 Fragment II, a new long-chain potassium channel toxin from Tityus serrulatus venom

Autor(es)

Cerni, Felipe Augusto ^[1] ; Pucca, Manuela Berto ^[1] ; Amorim, Fernanda Gobbi ^[1] ; Figueiredo Bordon, Karla de Castro ^[1] ; Echterbille, Julien ^[2] ; Quinton, Loic ^[2] ; De Pauw, Edwin ^[2] ; Peigneur, Steve ^[3] ; Tytgat, Jan ^[3] ; Arantes, Eliane Candiani ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Liege, Dept Chem, Lab Mass Spectrometry, Allee Chim 6, B6C, B-4000 Liege - Belgium

^[3] Univ Leuven, Toxicol & Pharmacol, O&N 2, Herestr 49, POB 922, B-3000 Leuven - Belgium

• Tipo de documento: Artigo Científico
• Fonte: Peptides; v. 80, p. 9-17, JUN 2016.
• Citações Web of Science: 11

Resumo

Ts19 Fragment II (Ts19 Frag-II) was first isolated from the venom of the scorpion Tityus serrulatus (Ts). It is a protein presenting 49 amino acid residues, three disulfide bridges, M-r 5534 Da and was classified as a new member of class (subfamily) 2 of the beta-KTxs, the second one described for Ts scorpion. The beta-KTx family is composed by two-domain peptides: N-terminal helical domain (NHD), with cytolytic activity, and a C-terminal CS alpha beta domain (CCD), with Kv blocking activity. The extensive electrophysiological screening (16 Kv channels and 5 Nav channels) showed that Ts19 Frag-II presents a specific and significant blocking effect on Kv1.2 (IC50 value of 544 +/- 32 nM). However, no cytolytic activity was observed with this toxin. We conclude that the absence of 9 amino acid residues from the N-terminal sequence (compared to Ts19 Frag-I) is responsible for the absence of cytolytic activity. In order to prove this hypothesis, we synthesized the peptide with these 9 amino acid residues, called Ts19 Frag-III. As expected, Ts19 Frag-III showed to be cytolytic and did not block the Kv1.2 channel. The post-translational modifications of Ts19 and its fragments (I-III) are also discussed here. A mechanism of post-translational processing (post-splitting) is suggested to explain Ts19 fragments production. In addition to the discovery of this new toxin, this report provides further evidence for the existence of several compounds in the scorpion venom contributing to the diversity of the venom arsenal. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 13/21342-7 - Caracterização eletrofisiológica da Ts19 fragmento II, uma nova toxina purificada da peçonha de Tityus serrulatus
• Beneficiário: Felipe Augusto Cerni
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 12/13590-8 - Isolamento, caracterização molecular e funcional de uma nova toxina presente na peçonha do escorpião Tityus serrulatus.
• Beneficiário: Felipe Augusto Cerni
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/21329-0 - Caracterização eletrofisiológica das toxinas provenientes da peçonha de Tityus serrulatus Ts3, Ts4, Ts6, Ts8, Ts15 e TS venom peptide 7: busca de novas drogas terapêuticas
• Beneficiário: Manuela Berto Pucca
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 13/26083-0 - Análise de modificações pós-traducionais de toxinas nativas e recombinantes da peçonha Tityus serrulatus por espectrometria de massas
• Beneficiário: Fernanda Gobbi Amorim
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 11/12317-3 - Clonagem e expressão heteróloga da hialuronidase e/ou novas toxinas obtidas a partir do transcriptoma da glândula da peçonha de Tityus serrulatus
• Beneficiário: Fernanda Gobbi Amorim
• Modalidade de apoio: Bolsas no Brasil - Doutorado