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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 10
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: Peptides; v. 80, p. 9-17, JUN 2016.
Web of Science Citations: 11
Abstract

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)

FAPESP's process: 13/21329-0 - Electrophysiological characterization of Tityus serrulatus venom toxins Ts3, Ts4, Ts6, Ts8, Ts15 and TS venom peptide 7: looking for new desired drugs
Grantee:Manuela Berto Pucca
Support type: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 13/26083-0 - Analysis of post-translational modifications of native and recombinant toxins from Tityus serrulatus venom by mass spectrometry
Grantee:Fernanda Gobbi Amorim
Support type: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 11/12317-3 - Cloning and heterologous expression of hyaluronidase and/or novel toxins obtained from the transcriptome of Tityus serrulatus' venom gland
Grantee:Fernanda Gobbi Amorim
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 12/13590-8 - Isolation, molecular and functional characterization of a new toxin from Tityus serrulatus scorpion venom
Grantee:Felipe Augusto Cerni
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/21342-7 - Electrophysiological characterization of Ts19 fragment II, a new toxin purified from Tityus serrulatus venom
Grantee:Felipe Augusto Cerni
Support type: Scholarships abroad - Research Internship - Doctorate