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Biophysical studies on protein P21 of Trypanosoma cruzi

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Author(s):
Francesco Brugnera Teixeira
Total Authors: 1
Document type: Doctoral Thesis
Press: São Carlos.
Institution: Universidade de São Paulo (USP). Instituto de Física de São Carlos
Defense date:
Examining board members:
Luiz Vitor de Souza Filho; Ana Paula Ulian de Araujo; Antônio José da Costa Filho; Fernando Alves de Melo; Tiago Venâncio
Abstract

According to the World Health Organization, in 2018, between 6 and 7 million people were still infected by the parasite Trypanosoma cruzi, the causative agent of Chagas disease. One of the worst aggravations for chagasics is heart disorder caused by the infection, which affects about 25% of patients in the chronic phase of the disease. Searching for biomolecules involved in the parasitic invasion of human cells, a T. cruzi protein called P21 was found. It has a high probability of being secreted or anchored to the membrane. Biological assays have shown that T. cruzi P21 interacts with the CXCR4 chemokine receptor and mediates several biochemical processes, such as: induction of phagocytosis by macrophages, induction of actin polymerization and inhibition of angiogenesis. The data suggests that P21 may also play a role in cardiomyopathy induced by parasite. In order to contribute to the biophysical and structural characterization of P21, a refolding protocol was developed to obtain P21 from inclusion bodies. The protocol provided the necessary amounts of protein required for the experiments. Nuclear Magnetic Resonance (NMR) spectra allowed to accurately evaluate the structural quality of the refolded sample in comparison to the produced soluble P21 protein. NMR spectra also showed five α-helices in the P21 secondary structure, a large unstructured portion and two ensembles of structures in equilibrium. Furthermore, corroborating with the biological data found in the literature, an in vitro interaction assay indicated that P21 interacts with CXCR4 via the N-terminal portion of the receptor. (AU)

FAPESP's process: 12/21153-7 - Structural studies on Trypanosoma cruzi P21 protein as a strategy for Chagas Disease treatment
Grantee:Francesco Brugnera Teixeira
Support type: Scholarships in Brazil - Doctorate (Direct)