Ligand Binding Promiscuity of Human Liver Fatty Acid Binding Protein: Structural and Dynamic Insights from an Interaction Study with Glycocholate and Oleate |
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| Authors: | Filippo Favretto Dr Michael Assfalg Dr Mariana Gallo Prof Daniel Oscar Cicero Dr Mariapina D'Onofrio Prof Henriette Molinari |
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| Affiliation: | 1. NMR laboratory, Department of Biotechnology, University of Verona, Strada le Grazie 15, 37134 Verona (Italy);2. Fundación Instituto Leloir, IIBBA‐CONICET, Patricias Argentinas 435, C1405BWE Buenos Aires (Argentina);3. Department of Chemical Science and Technology, University of Rome “Tor Vergata” via della Ricerca Scientifica 1, 00133 Rome (Italy);4. Laboratorio NMR, ISMAC‐CNR, Via Bassini 15, 20133 Milano (Italy) |
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| Abstract: | Human liver fatty acid binding protein (hL‐FABP) has been reported to act as an intracellular shuttle of lipid molecules, thus playing a central role in systemic metabolic homeostasis. The involvement of hL‐FABP in the transport of bile salts has been postulated but scarcely investigated. Here we describe a thorough NMR investigation of glycocholate (GCA) binding to hL‐FABP. The protein molecule bound a single molecule of GCA, in contrast to the 1:2 stoichiometry observed with fatty acids. GCA was found to occupy the large internal cavity of hL‐FABP, without requiring major conformational rearrangement of the protein backbone; rather, this led to increased stability, similar to that estimated for the hL‐FABP:oleate complex. Fast‐timescale dynamics appeared not to be significantly perturbed in the presence of ligands. Slow motions (unlike for other proteins of the family) were retained or enhanced upon binding, consistent with a requirement for structural plasticity for promiscuous recognition. |
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| Keywords: | bile salts dynamics fatty acids intracellular lipid transport NMR spectroscopy |
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