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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Autores principales: | , , , , , , , , , , |
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Formato: | Articulo |
Lenguaje: | Inglés |
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2015
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Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/86299 |
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I19-R120-10915-86299 |
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institution |
Universidad Nacional de La Plata |
institution_str |
I-19 |
repository_str |
R-120 |
collection |
SEDICI (UNLP) |
language |
Inglés |
topic |
Ciencias Médicas Fatty acid-binding protein Necator americanus Nematode Nuclear magnetic resonance (NMR) Parasite Protein structure Retinol-binding protein X-ray |
spellingShingle |
Ciencias Médicas Fatty acid-binding protein Necator americanus Nematode Nuclear magnetic resonance (NMR) Parasite Protein structure Retinol-binding protein X-ray 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. Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanus |
topic_facet |
Ciencias Médicas Fatty acid-binding protein Necator americanus Nematode Nuclear magnetic resonance (NMR) Parasite Protein structure Retinol-binding protein X-ray |
description |
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. |
format |
Articulo Articulo |
author |
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. |
author_facet |
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. |
author_sort |
Rey Burusco, M. F. |
title |
Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanus |
title_short |
Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanus |
title_full |
Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanus |
title_fullStr |
Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanus |
title_full_unstemmed |
Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanus |
title_sort |
diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by na-far-1 from necator americanus |
publishDate |
2015 |
url |
http://sedici.unlp.edu.ar/handle/10915/86299 |
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Repositorios |
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1764820489541255171 |