4UET

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

Summary for 4UET

• Entry DOI: 10.2210/pdb4uet/pdb
• NMR Information: BMRB: 18637
• Descriptor: NEMATODE FATTY ACID RETINOID BINDING PROTEIN (1 entity in total)
• Functional Keywords: retinol-binding protein, fatty acid binding, retinol binding, all-alpha
• Biological source: NECATOR AMERICANUS
• Total number of polymer chains: 1
• Total formula weight: 18803.53

Authors

Rey-Burusco, M.F.,Ibanez Shimabukuro, M.,Griffiths, K.,Cooper, A.,Kennedy, M.W.,Corsico, B.,Smith, B.O.,Griffiths, K. (deposition date: 2014-12-18, release date: 2015-09-16, Last modification date: 2024-05-15)

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-, 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

SOLUTION NMR