Fatty acid binding proteins (FABPs) act as intracellular carriers of lipid molecules, and play a role in global metabolism regulation. Liver FABP (L-FABP) is characterized by high versatility in terms of ligand binding capabilities.[1] Indeed, both long chain fatty acids as well as bulkier ligands can be accommodated into the protein’s large internal cavity. The involvement of L-FABP in the transport of bile salts has been postulated but scarcely investigated.[2] This hypothesis is further supported by the realization that L-BABP (a type 2 intracellular lipid binding protein bile-salt carrier) is absent in mammals. We have used a variety of NMR experiments, as well as steady-state fluorescence spectroscopy, and mass spectrometry to gain insight, at molecular and atomic level, into the interactions established by human L-FABP with a pool of bile acids [3, 4], contributing to improve our understanding of the binding specificity for this important class of cholesterol-derived metabolites. An extensive comparison among L-FABP alone, in complex with bile acids, and in complex with oleate, has been performed in order to investigate the distinctive features of L-FABP binding promiscuity.[3] NMR relaxation experiments on different timescales suggest that human L-FABP is poorly selective in terms of ligand binding and a functional role is played by its internal dynamics. Taken together our findings expand the current knowledge about ligand recognition by L-FABP with implications in the intracellular transport of bile acids in physiological and pathological states.

Understanding promiscuous and selective ligand binding by liver FABP

D'ONOFRIO, Mariapina;Favretto, Filippo;ZANZONI, Serena;ASSFALG, Michael;MOLINARI, Henriette;
2015-01-01

Abstract

Fatty acid binding proteins (FABPs) act as intracellular carriers of lipid molecules, and play a role in global metabolism regulation. Liver FABP (L-FABP) is characterized by high versatility in terms of ligand binding capabilities.[1] Indeed, both long chain fatty acids as well as bulkier ligands can be accommodated into the protein’s large internal cavity. The involvement of L-FABP in the transport of bile salts has been postulated but scarcely investigated.[2] This hypothesis is further supported by the realization that L-BABP (a type 2 intracellular lipid binding protein bile-salt carrier) is absent in mammals. We have used a variety of NMR experiments, as well as steady-state fluorescence spectroscopy, and mass spectrometry to gain insight, at molecular and atomic level, into the interactions established by human L-FABP with a pool of bile acids [3, 4], contributing to improve our understanding of the binding specificity for this important class of cholesterol-derived metabolites. An extensive comparison among L-FABP alone, in complex with bile acids, and in complex with oleate, has been performed in order to investigate the distinctive features of L-FABP binding promiscuity.[3] NMR relaxation experiments on different timescales suggest that human L-FABP is poorly selective in terms of ligand binding and a functional role is played by its internal dynamics. Taken together our findings expand the current knowledge about ligand recognition by L-FABP with implications in the intracellular transport of bile acids in physiological and pathological states.
2015
FABP, NMR, mass spectrometry, ligand binding
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/932631
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