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.

Favretto, F., Assfalg, M., Gallo, M., Cicero, D.o., D'Onofrio, M., Molinari, H. (2013). Ligand binding promiscuity of human liver fatty acid binding protein: structural and dynamic insights from an interaction study with glycocholate and oleate. CHEMBIOCHEM, 14, 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

CICERO, DANIEL OSCAR;
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
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Favretto, F., Assfalg, M., Gallo, M., Cicero, D.o., D'Onofrio, M., Molinari, H. (2013). Ligand binding promiscuity of human liver fatty acid binding protein: structural and dynamic insights from an interaction study with glycocholate and oleate. CHEMBIOCHEM, 14, 1807-1819 [10.1002/cbic.201300156].
Favretto, F; Assfalg, M; Gallo, M; Cicero, Do; D'Onofrio, M; Molinari, H
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/87949
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