Publication

Article Metrics

Citations


Online attention

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

DOI: 10.1042/BJ20150068 DOI Help
PMID: 26318523 PMID Help

Authors: M. F. Rey Burusco (Facultad de Ciencias Médicas) , M. Ibanez Shimabukuro (Facultad de Ciencias Médicas) , M. Gabrielsen (University of Glasgow) , G. R. Franchini (Facultad de Ciencias Médicas) , A. J. Roe (University of Glasgow) , K. Griffiths (University of Glasgow) , B. Zhan (Baylor College of Medicine,) , A. Cooper (University of Glasgow) , M. W. Kennedy (University of Glasgow) , B. Corsico (Facultad de Ciencias Médicas) , B. O. Smith (University of Glasgow)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biochemical Journal

State: Published (Approved)
Published: August 2015
Diamond Proposal Number(s): 1229

Open Access Open Access

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 α-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 α-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.

Subject Areas: Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography

Discipline Tags:



Technical Tags: