CONICET | Buscador de Institutos y Recursos Humanos

Structural and biophysical analysis of novel lipid binding proteins from parasitic helminths. Ibañez, M.; Rey F.; Pórfido, J.; Silva, V. ; Franchini, GR. and Córsico, B. Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP) (CONICET-UNLP), Fac. de Cs. Médicas, Calle 60 y 120 (1900) La Plata. Parasitic helminths secrete 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 and phospholipids. LBPs functions in parasite biology are still unknown, although it is generally assumed that they play a role 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 of which 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. Characterization of ligand-bound states has shown evidence of conformational changes. We are also analyzing their ligand-binding properties employing fluorescence-based systems and ITC. The studies confirm these LBPs bind natural ligands and fluorescent analogues with high affinity. The results of the present work constitute a first step in the understanding of the function of LBPs in the parasitic biology.