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, B. M.F. et al. (2015) Diversity in the structures and ligand binding sites of nematode fatty acid and retinol binding proteins revealed by Na-FAR-1 from Necator americanus. Biochemical Journal, 471(3), pp. 403-414. (doi: 10.1042/BJ20150068) (PMID:26318523) (PMCID:PMC4613501)

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Fatty acid and retinol binding proteins (FARs) comprise a family of unusual α-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 (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 Na-FAR-1 from the blood-feeding intestinal parasite of humans, Necator americanus . The three dimensional structure of Na-FAR-1 in its ligand-free and ligand-bound forms, determined by nuclear magnetic resonance spectroscopy (NMR) 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 ligand binding 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 here by our finding that a range of neutral and polar lipids co-purify with the bacterial 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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Kennedy, Professor Malcolm and Griffiths, Mrs Kate and Roe, Professor Andrew and Franchini, Dr Gisela and Smith, Dr Brian and Cooper, Professor Alan
Authors: Rey, B. M.F., Ibáñez, S. M., Gabrielsen, M., Franchini, G. R., Roe, A. J., Griffiths, K., Zhan, B., Cooper, A., Kennedy, M. W., Córsico, B., and Smith, B. O.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
College of Science and Engineering > School of Chemistry
Journal Name:Biochemical Journal
Publisher:Portland Press
ISSN (Online):1470-8728
Published Online:28 August 2015
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Biochemical Journal 471(3):403-414
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
465741Structural and biophysical analysis of novel lipid binding proteins from parasitic helminthsMalcolm KennedyWellcome Trust (WELLCOME)083625/Z/07/ZLS - ANIMAL BIOLOGY
491441A biochemical and molecular analysis of the YhaO membrane protein in Escherichia coli O157:H7Andrew RoeBiotechnology and Biological Sciences Research Council (BBSRC)BB/G011389/1III - BACTERIOLOGY