Soluble lipid binding proteins of parasitic Helminths with clinical relevance: From structure to function.

B. CÓRSICO

Mar del Plata

Congreso; IX Congreso Argentino de Protozoología y Enfermedades Parasitarias; 2011

SAP

Parasitic helminths express lipid-binding proteins (LBPs) that are structurally distinct from host LBPs. These proteins bind a wide range of lipid classes such as fatty acids, retinoids, eicosanoids, triglycerides, phospholipids and cholesterol. Due to helminth’s limited lipid metabolism, LBP’s have been proposed to participate in parasites development and in parasite-host interactions. To understand the mechanisms involved, we have selected three important types of LBPs from highly pathogenic helminth parasites: a) a novel class of fatty acid and retinol binding proteins with a structure that has no known counterpart, b) relatives of the fatty acid binding protein family, including members that are structurally modified in ways that are unique to nematodes, and c) Antigen B, a member of a new family of ligand binding proteins present in cestodes. Their atomic structures are under analysis employing NMR spectroscopy, for which we already have obtained high quality data and full structure determination is in progress. Specifically for As-p18, a member of the nematode FABP family of proteins, 88% of the backbone´s protein structure has been asigned so far, along with the 65% of the side chain H. Protein's interactions with ligands employing NMR spectra show the changes registered during the binding process when stripped and reloaded samples are compared. We are also analyzing their ligand-binding binding parameters (n, K, ∆H and ΔS). employing fluorescence-based systems and ITC. The studies confirm these LBPs bind natural ligands and fluorescent analogues with high affinity (in the sub-micromolar range). The results of the present work constitute a first step in the understanding of the function of LBPs in the parasitic biology. Structural and functional studies will enhance our understanding of the unique features of helminth LBPs that may be related to the survival of the organisms and could be used as potential drug targets.