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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Abstract
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 |
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| Status: | Published |
| Refereed: | Yes |
| 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: | 0264-6021 |
| 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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