Structural study of the interaction of crotoxin and their subunits with model membranes and inhibitors

• Grant number: 18/05090-1
• Support type: Scholarships in Brazil - Master
• Effective date (Start): May 01, 2018
• Effective date (End): February 29, 2020
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal researcher: Marcos Roberto de Mattos Fontes
• Grantee: Carlos Roberto Natal Junior
• Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Crotoxin (CTX) is the most abundant toxin present in the venom of Crotalus durissus terrificus, accounting for about 60 per cent of the dry venom weight of this snake. CTX has neurotoxic, myotoxic and coagulant activities and it is the main responsible for the high number of death by ophidian accidents caused by snakes of the genus Crotalus. In addition to those characteristics, it was discovered actions of crotoxin with possible therapeutic applications due to their anti-inflammatory, analgesic, immunomodulatory and antitumor effects. CTX is a heterodimer composed of two subunits, one acid (CA) and one basic (CB). CB is a phospholipase A2 with presynaptic activity of neuromuscular transmission blockade that causes motor and respiratory paralysis in animals. Although crystallographic and small angle X-ray scattering structures of CTX and CB have been resolved, their mechanism of action as well as the location of interaction sites of these proteins with target membranes is still little known. We propose in this work structural studies of crotoxin and its subunits on model membranes and about the interaction of their with different inhibitors. We will use the techniques of fluorescence spectroscopy, small angle x-ray scattering, isothermal titration calorimetry and protein crystallography. Thus, we expect to propose a model of action of crotoxin and its subunits and to identify the interaction sites of these proteins with target membranes. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

JUNIOR, Carlos Roberto Natal. Estudo estrutural da interação da crotoxina e suas subunidades com membranas modelo. 2020. Master's Dissertation - Universidade Estadual Paulista "Júlio de Mesquita Filho" Instituto de Biociências (Campus de Botucatu)..