Structural and biophysical analysis of novel lipid binding proteins from parasitic helminths.

MARINA IBAÑEZ SHIMABUKURO; MARÍA FLORENCIA REY; JORGE LUIS PÓRFIDO; VALERIA SILVA; GISELA R. FRANCHINI; BETINA CÓRSICO

Facultad de Farmacia y Bioquímica UBA

Jornada; HERRAMIENTAS MODERNAS PARA EL ESTUDIO DE ASPECTOS ESTRUCTURALES DE PROTEÍNAS”; 2009

ACADEMIA NACIONAL DE FARMACIA Y BIOQUÍMICA

Parasitic helminths secrete lipid-binding proteins (LBPs) that are structurally distinctfrom 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 stillunknown, although it is generally assumed that they play a role in parasite-hostinteractions. To understand the mechanisms involved, we have selected three importanttypes of LBPs from highly pathogenic helminth parasites: a) a novel class of fatty acidand retinol binding proteins with a structure that has no known counterpart, b) relativesof the fatty acid binding protein family of which are structurally modified in ways thatare unique to nematodes, and c) Antigen B, a member of a new family of ligand bindingproteins present in cestodes. Their atomic structures are under analysis employing NMRspectroscopy, for which we already have obtained high quality data and full structuredetermination is in progress. Characterization of ligand-bound states has shownevidence of conformational changes. We are also analyzing their ligand-bindingproperties employing fluorescence-based systems and ITC. The studies confirm theseLBPs bind natural ligands and fluorescent analogues with high affinity. The results ofthe present work constitute a first step in the understanding of the function of LBPs inthe parasitic biology.