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. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ligand binding promiscuity of human liver fatty acid binding protein: Structural and dynamic insights from an interaction study with glycocholate and oleate / Favretto, F.; Assfalg, M.; Gallo, M.; Cicero, D. O.; D'Onofrio, M.; Molinari, H.. - In: CHEMBIOCHEM. - ISSN 1439-4227. - 14:14(2013), pp. 1807-1819. [10.1002/cbic.201300156]

Ligand binding promiscuity of human liver fatty acid binding protein: Structural and dynamic insights from an interaction study with glycocholate and oleate

Gallo M.;
2013-01-01

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. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
2013
Ligand binding promiscuity of human liver fatty acid binding protein: Structural and dynamic insights from an interaction study with glycocholate and oleate / Favretto, F.; Assfalg, M.; Gallo, M.; Cicero, D. O.; D'Onofrio, M.; Molinari, H.. - In: CHEMBIOCHEM. - ISSN 1439-4227. - 14:14(2013), pp. 1807-1819. [10.1002/cbic.201300156]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2878192
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