Structures of the nematode-specific FAR-1 and nemFABP lipid binding proteins

MALCOLM W. KENNEDY; MARINA IBÁÑEZ SHIMABUKURO; M. FLORENCIA REY BURUSCO; MADS GABRIELSEN; ALAN COOPER; BRIAN O. SMITH; BETINA CÓRSICO

Isla Hydra

Congreso; Molecular and Cellular Biology of Helminths VII; 2012

We previously reported on the binding and structural characteristics of two families of proteins that are unique to nematodes: the nematode fatty acid binding proteins (nemFABPs) and the fatty acid and retinol binding proteins (FARs). The nemFABPs are similar to mammalian cellular fatty acid binding proteins but have unusual structural features, and only in nematodes are they secreted from the synthesising cells. They are abundant in perivitelline fluid of nematode eggs (e.g. Ascaris and Brugia), so may be essential to the lipid requirements of developing infective larvae. We present protein nuclear magnetic resonance (NMR) and x-ray crystallographic structures of a nemFABP (As-p18 found in the perivitelline fluid of Ascaris eggs) that indeed exhibits novel structural modifications. These modifications were not predicted in previous model building, despite the relative simplicity of the modeling task. The other unusual nematode-specific lipid binding proteins, the FARs, are helix-rich, bind hydrophobic ligands, and are abundant in the secretions of both animal and plant parasites, with possible importance in modifying lipid-based signaling systems in parasitised tissues. Here we present the protein NMR and x-ray crystallographic structures of a FAR that was identified form EST surveys from the hookworm Necator americanus. In both cases, preferred ligands were analysed by TLC and GC, as well as the number of binding sites by NMR.