Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanus

Fatty acid and retinol-binding proteins (FARs) comprise a family of unusual a-helix rich lipid-binding proteins found exclusively in nematodes. They are secreted into host tissues by parasites of plants, animals and humans. The structure of a FAR protein from the free-living nematode Caenorhabditis...

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Detalles Bibliográficos
Autores principales: Rey Burusco, M. F., Ibáñez Shimabukuro, Marina, Gabrielsen, M., Franchini, Gisela Raquel, Roe, A. J., Griffiths, K., Zhan, B., Cooper, A., Kennedy, M. W., Córsico, Betina, Smith, B. O.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2015
Materias:
Ciencias Médicas
Fatty acid-binding protein
Necator americanus
Nematode
Nuclear magnetic resonance (NMR)
Parasite
Protein structure
Retinol-binding protein
X-ray
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/86299
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
Descripción
Sumario:Fatty acid and retinol-binding proteins (FARs) comprise a family of unusual a-helix rich lipid-binding proteins found exclusively in nematodes. They are secreted into host tissues by parasites of plants, animals and humans. The structure of a FAR protein from the free-living nematode Caenorhabditis elegans is available, but this protein [C. elegans FAR-7 (Ce-FAR-7)] is from a subfamily of FARs that does not appear to be important at the host/parasite interface. We have therefore examined [Necator americanus FAR-1 (Na-FAR-1)] from the blood-feeding intestinal parasite of humans, N. americanus. The 3D structure of Na-FAR-1 in its ligand-free and ligand-bound forms, determined byNMR(nuclear magnetic resonance) spectroscopy and X-ray crystallography respectively, reveals an a-helical fold similar to Ce-FAR-7, but Na-FAR-1 possesses a larger and more complex internal ligandbinding cavity and an additional C-terminal a-helix. Titration of apo-Na-FAR-1 with oleic acid, analysed by NMR chemical shift perturbation, reveals that at least four distinct protein-ligand complexes can be formed. Na-FAR-1 and possibly other FARs may have a wider repertoire for hydrophobic ligand binding, as confirmed in the present study by our finding that a range of neutral and polar lipids co-purify with the bacterially expressed recombinant protein. Finally, we show by immunohistochemistry that Na-FAR-1 is present in adult worms with a tissue distribution indicative of possible roles in nutrient acquisition by the parasite and in reproduction in the male.

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