Structural, functional and bioprospecting studies of recombinant Ts16 toxin

• Grant number: 24/17849-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2024
• End date: November 30, 2027
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Eliane Candiani Arantes Braga
• Grantee: Beatriz de Cássia da Silva Jacob
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 21/11936-3 - Center for Translational Science and Biopharmaceutical Development, AP.CCD

Abstract

Potassium channel-specific scorpion toxins (KTx) are usually small, basic peptides made up of 23-43 amino acids stabilized by 3-4 disulfide bonds. KTx are classified into 6 subfamilies. The Ts16 toxin, isolated from the scorpion Tityus serrulatus, was partially characterized in 2011, demonstrating selectivity for potassium channels of the Kv1 subtype.2. In the same year, another study suggested that this toxin presents an unprecedented topology, with a connectivity between the disulfide bonds never described. However, additional experiments are needed to confirm these findings. In this sense, the objective of this work is the heterologous expression of the toxin Ts16, a novel neurotoxin selective for Kv1.2 channels, in a system in Pichia pastoris cells. With the success of heterologous expression of Ts16, larger amounts of the toxin will be made available for the performance of additional functional and structural experiments, necessary for the development of the toxin. In addition to the heterologous expression of Ts16, a structural comparison between the native and recombinant forms, with techniques that require little amount of toxin is also the purpose of this project. After comparison, the electrophysiological activity and anti-tumor potential will be performed with the recombinant Ts16.