title: Ligand binding promiscuity of human liver fatty acid binding protein: structural and dynamic insights from an interaction study with glycocholate and oleate.
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.
authors.affiliation: NMR laboratory, Department of Biotechnology, University of Verona, Strada le Grazie 15, 37134 Verona (Italy).
authors.forename: Filippo
authors.initials: F
authors.lastname: Favretto
authors.forename: Michael
authors.initials: M
authors.lastname: Assfalg
authors.forename: Mariana
authors.initials: M
authors.lastname: Gallo
authors.forename: Daniel Oscar
authors.initials: DO
authors.lastname: Cicero
authors.forename: Mariapina
authors.initials: M
authors.lastname: D'Onofrio
authors.forename: Henriette
authors.initials: H
authors.lastname: Molinari
mesh_terms: D001665:Binding Sites; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006000:Glycocholic Acid / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular; D019301:Oleic Acid / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics
chemical_list: D050556:Fatty Acid-Binding Proteins; D008024:Ligands; D011994:Recombinant Proteins; D019301:Oleic Acid; D006000:Glycocholic Acid
keywords: NMR spectroscopy; bile salts; dynamics; fatty acids; intracellular lipid transport