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, 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 proved able to bind a single molecule of GCA in contrast with the 1:2 stoichiometry observed with fatty acids. GCA was found to occupy the large internal cavity of hL-FABP without requiring major conformational rearrangements of the protein backbone but leading to an increased stability, similar to that estimated for the hL-FABP:oleate complex. Fast time scale dynamics appeared not significantly perturbed in the presence of ligands. Slow motions, at variance with other proteins of the family, were retained or enhanced upon binding and consistent with a requirement of structural plasticity for promiscuous recognition.