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

Autores
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.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Instituto de Investigaciones Bioquímicas de La Plata
Materia
Ciencias Médicas
Fatty acid-binding protein
Necator americanus
Nematode
Nuclear magnetic resonance (NMR)
Parasite
Protein structure
Retinol-binding protein
X-ray
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/3.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/86299

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spelling Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanusRey Burusco, M. F.Ibáñez Shimabukuro, MarinaGabrielsen, M.Franchini, Gisela RaquelRoe, A. J.Griffiths, K.Zhan, B.Cooper, A.Kennedy, M. W.Córsico, BetinaSmith, B. O.Ciencias MédicasFatty acid-binding proteinNecator americanusNematodeNuclear magnetic resonance (NMR)ParasiteProtein structureRetinol-binding proteinX-rayFatty 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.Instituto de Investigaciones Bioquímicas de La Plata2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf403-414http://sedici.unlp.edu.ar/handle/10915/86299enginfo:eu-repo/semantics/altIdentifier/issn/0264-6021info:eu-repo/semantics/altIdentifier/doi/10.1042/BJ20150068info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/Creative Commons Attribution 3.0 Unported (CC BY 3.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:16:54Zoai:sedici.unlp.edu.ar:10915/86299Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:16:54.472SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv 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 Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanus
spellingShingle Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanus
Rey Burusco, M. F.
Ciencias Médicas
Fatty acid-binding protein
Necator americanus
Nematode
Nuclear magnetic resonance (NMR)
Parasite
Protein structure
Retinol-binding protein
X-ray
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
dc.creator.none.fl_str_mv 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 Rey Burusco, M. F.
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_role author
author2 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.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
Fatty acid-binding protein
Necator americanus
Nematode
Nuclear magnetic resonance (NMR)
Parasite
Protein structure
Retinol-binding protein
X-ray
topic Ciencias Médicas
Fatty acid-binding protein
Necator americanus
Nematode
Nuclear magnetic resonance (NMR)
Parasite
Protein structure
Retinol-binding protein
X-ray
dc.description.none.fl_txt_mv 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.
Instituto de Investigaciones Bioquímicas de La Plata
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.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
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Creative Commons Attribution 3.0 Unported (CC BY 3.0)
eu_rights_str_mv openAccess
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