Novel lipid binding proteins from helminth parasites. Structural and functional analysis

BETINA CÓRSICO

Carlos Paz

Congreso; XLII Reunión Anual de la Sociedad Argentina de Biofisica; 2013

SAB

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 the interaction with the host. 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) nematode polyprotein allergens. The atomic structures are under analysis employing NMR spectroscopy, for which we already have obtained high quality data and full structure determination is in progress. 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 parameters employing fluorescence-based systems. The studies confirm these LBPs bind natural ligands and fluorescent analogues in the sub-micromolar range. 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