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

Ibáñez-Shimabukuro, M. et al. (2019) Structure and ligand binding of As-p18, an extracellular fatty acid binding protein from the eggs of a parasitic nematode. Bioscience Reports, 39(7), BSR2019129. (doi: 10.1042/BSR20191292) (PMID:31273060) (PMCID:PMC6646235)

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Intracellular 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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Kennedy, Professor Malcolm and Griffiths, Mrs Kate and Riboldi-Tunnicliffe, Dr Alan and Gabrielsen, Dr Mads and Roe, Professor Andrew and Franchini, Dr Gisela and Smith, Dr Brian and Cooper, Professor Alan
Authors: Ibáñez-Shimabukuro, M., Rey-Burusco, M. F., Gabrielsen, M., Franchini, G. R., Riboldi-Tunnicliffe, A., Roe, A. J., Griffiths, K., Cooper, A., Córsico, B., Kennedy, M. W., 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:Bioscience Reports
Publisher:Portland Press
ISSN (Online):1573-4935
Published Online:04 July 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Bioscience Reports 39(7): BSR2019129
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
465741Structural and biophysical analysis of novel lipid binding proteins from parasitic helminthsMalcolm KennedyWellcome Trust (WELLCOTR)083625/Z/07/ZLS - ANIMAL BIOLOGY
491441A biochemical and molecular analysis of the YhaO membrane protein in Escherichia coli O157:H7Andrew RoeBiotechnology and Biological Sciences Research Council (BBSRC)BB/G011389/1III - BACTERIOLOGY