The liver fatty acid binding protein — comparison of cavity properties of intracellular lipid-binding proteins

The physiological role of liver fatty acid-binding protein (L-FABP) has yet to be clarified. An important feature of this member of the family of intracellular lipid-binding proteins is the wide range of compounds that have been identified as potential physiological ligands. By using recombinant L-FABP, the binding of cholesterol, bile salts and their derivatives has been investigated under conditions that allow a direct comparison of the binding affinities of these ligands for fatty acids. The results demonstrate an inability of L-FABP to bind cholesterol, although the anionic derivative, cholesteryl sulphate, will bind under similar assay conditions. Of the bile salts examined, lithocholate and taurolithocholate sulphate showed the greatest binding to L-FABP. It is proposed that an important function of L-FABP is to bind certain physiological amphipathic anions, thus preventing the ‘free’ concentrations of these compounds from exceeding their critical micelle concentration, which could result in cell damage.

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Structure and ligand binding of As-p18, an extracellular fatty acid binding protein from the eggs of a parasitic nematode

Bioscience Reports ◽

10.1042/bsr20191292 ◽

2019 ◽

Vol 39 (7) ◽

Author(s):

Marina Ibáñez-Shimabukuro ◽

M. Florencia Rey-Burusco ◽

Mads Gabrielsen ◽

Gisela R. Franchini ◽

Alan Riboldi-Tunnicliffe ◽

...

Keyword(s):

Fatty Acid ◽

Binding Proteins ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Structural Features ◽

Lipid Binding ◽

Head Group ◽

Resonance Spectroscopy ◽

Fatty Acid Binding ◽

Acid Binding Protein

AbstractIntracellular lipid-binding proteins (iLBPs) of the fatty acid-binding protein (FABP) family of animals transport, mainly fatty acids or retinoids, are confined to the cytosol and have highly similar 3D structures. In contrast, nematodes possess fatty acid-binding proteins (nemFABPs) that are secreted into the perivitelline fluid surrounding their developing embryos. We report structures of As-p18, a nemFABP of the large intestinal roundworm Ascaris suum, with ligand bound, determined using X-ray crystallography and nuclear magnetic resonance spectroscopy. In common with other FABPs, As-p18 comprises a ten β-strand barrel capped by two short α-helices, with the carboxylate head group of oleate tethered in the interior of the protein. However, As-p18 exhibits two distinctive longer loops amongst β-strands not previously seen in a FABP. One of these is adjacent to the presumed ligand entry portal, so it may help to target the protein for efficient loading or unloading of ligand. The second, larger loop is at the opposite end of the molecule and has no equivalent in any iLBP structure yet determined. As-p18 preferentially binds a single 18-carbon fatty acid ligand in its central cavity but in an orientation that differs from iLBPs. The unusual structural features of nemFABPs may relate to resourcing of developing embryos of nematodes.

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