Structure and ligand binding properties of Na-FAR-1, a hookworm fatty acid and retinol binding protein

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

San Javier, Tucumán

Congreso; XLI Reunión Anual de la Sociedad Argentina de Biofísica; 2012

FARs are -helix-rich proteins of around 20 kDa that are produced at different life cycle stages of nematodes and have been observed to be secreted by adult parasites (Basavaraju et al. 2003; Kennedy et al. 1997; Prior et al. 2001). It is hypothesized that FARs may play a role in host-parasite interaction and pathogenesis by sequestering or delivering lipid mediators, thereby affecting the local tissue environment of the host, and compromising immune and inflammatory defences (Bradley et al. 2001). FAR proteins are already used as diagnostic tools (Burbelo et al. 2009), and have also been shown to induce immunity against one parasite infection (Fairfax et al, 2009). They are, therefore, attractive potential targets for drug or vaccine development because they have no structural counterparts in mammals (Basavaraju et al. 2003). Na-FAR-1 is Na-FAR-1 is has been identified in a transcriptomic survey of N. americanus (Daub et al. 2000), and we here report resonance assignments of its bacterial recombinant form. The only structure of a FAR currently available is a crystal structure of Ce-FAR-7 of the free living nematode Caenorhabditis elegans (Jordanova et al. 2009). This FAR has seven -helixes and comprises two binding sites that could accommodate different types of ligands. We find that Na-FAR-1 has a similar overall arrangement of regular secondary structure elements, but with an extra helical region at the C-terminus.