Structural and functional studies of a hypothetical fatty acid binding protein in Leishmania amazonensis

• Grant number: 23/02831-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2023
• End date: May 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Roberto Kopke Salinas
• Grantee: Lucas Felipe Almeida Athayde
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leishmaniasis is a class of neglected diseases caused by different species of the Leishmania genus, of the Trypanosomatidae family. The hypothetical protein encoded by the LmxM.34.3070 gene was first identified in Leishmania mexicana. Using the amino acid sequence of LmxM.34.3070, structure predictions by different methods (PHYRE2, RaptorX, and AlphaFold) pointed out the presence of a domain structurally similar to the fatty acids binding proteins (FABP). These results suggest that LmxM.34.3070 could be associated with the metabolism of lipids and fatty acids, which is essential for Leishmania survival in the host environment. Furthermore, similarity searches revealed that LmxM.34.307 is conserved among Leishmania spp. and other trypanosomatids. In this project we will characterize the biological function of LmxM.34.3070 by phenotypic analysis of knockouts in Leishmania amazonensis obtained by the CRISPR/Cas9 technique. We will solve LmxM.34.3070 protein structure using a combination of NMR with X-ray crystallography, and identify the natural ligand. We expect that this combination of cell biology and structural biology approaches will allow us to uncover the biological function of LmxM34.3070 and its potential role in Leishmania fatty acid metabolism.