Soluble lipid binding proteins from relevant parasitic helminths: From structure to function

MARINA IBAÑEZ SHIMABUKURO; MARÍA FLORENCIA REY; JORGE LUIS PÓRFIDO; VALERIA SILVA; GISELA R. FRANCHINI; MALCOLM W. KENNEDY; ALAN COOPER; BRIAN SMITH; BETINA CÓRSICO

Waterville Valley, New Hampshire

Conferencia; GRC Molecular and Cell Biology of Lipids; 2011

Gordon Research Conferences

Infections with parasitic helminths cause severe debilitating and sometimes lethal diseases in humans and domestic animals on a global scale. Unable to synthesize their own fatty acids and sterols, helminth parasites (nematodes, trematodes, cestodes) rely on their hosts for their supply. The acquisition and transport of lipids is crucial to these organisms, and the proteins and their receptors involved in lipid transport and exchange provide potential targets for chemo- and immunotherapy. Helminths produce and secrete a wide range of novel lipid binding proteins (LBP), most of them structurally distinct from those of their hosts. These proteins bind several lipid classes such as fatty acids, retinoids, eicosanoids, triglycerides, phospholipids and cholesterol. Four important types of LBPs from highly pathogenic helminth parasites have been selected: a) a novel class of fatty acid and retinol binding protein 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, c) Antigen B, a member of a new family of ligand binding proteins present in cestodes, and d) nematode polyprotein allergens/antigens. Their atomic structures are under analysis employing NMR spectroscopy, for which high quality data have already been obtained and full structure calculation is in progress. Protein-ligand interactions have also been studied by NMR, observing changes in NMR spectra, when stripped and reloaded samples are compared, evidencing conformational changes produced during the binding process. We are also analyzing their ligand-binding parameters (n, K, ∆H and ΔS) employing fluorescence-based systems and ITC. The studies confirm these LBPs bind natural ligands and fluorescent analogues in the sub-micromolar range. Additionally, protein-membrane interaction assays are being performed in vitro in order to characterize LBPs? possible functions. 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.