4XCP

Fatty Acid and Retinol binding protein Na-FAR-1 from Necator americanus

Summary for 4XCP

• Entry DOI: 10.2210/pdb4xcp/pdb
• Descriptor: Nematode fatty acid retinoid binding protein, PALMITIC ACID (3 entities in total)
• Functional Keywords: fatty acid retinol binding, retinol-binding protein
• Biological source: Necator americanus (Human hookworm)
• Total number of polymer chains: 1
• Total formula weight: 19550.86

Authors

Gabrielsen, M.,Rey-Burusco, M.F.,Ibanez-Shimabukuro, M.,Griffiths, K.,Kennedy, M.W.,Corsico, B.,Smith, B.O. (deposition date: 2014-12-18, release date: 2015-09-16, Last modification date: 2024-10-23)

Primary citation

Rey-Burusco, M.F.,Ibanez-Shimabukuro, M.,Gabrielsen, M.,Franchini, G.R.,Roe, A.J.,Griffiths, K.,Zhan, B.,Cooper, A.,Kennedy, M.W.,Corsico, B.,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.
Biochem.J., 471:403-414, 2015

PubMed 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 [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 by NMR (nuclear magnetic resonance) spectroscopy 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 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.

PubMed: 26318523
DOI: 10.1042/BJ20150068

Experimental method

X-RAY DIFFRACTION (2.14 Å)