title: The unique ligand binding features of subfamily-II iLBPs with respect to bile salts and related drugs.
abstract: Intracellular lipid binding proteins (iLBPs) are a family of evolutionarily related small cytoplasmic proteins implicated in the transcellular transport of lipophilic ligands. Subfamily-II iLBPs include the liver fatty acid binding protein (L-FABP), and the ileal and the liver and ileal bile acid binding proteins (L-BABP and I-BABP). Atomic-level investigations during the past 15-20 years have delivered relevant information on bile acid binding by this protein group, revealing unique features including binding cooperativity, promiscuity, and site selectivity. Using NMR spectroscopy and other biophysical techniques, our laboratories have contributed to an understanding of the molecular determinants of some of these properties and their generality among proteins from different animal species. We focused especially on formation of heterotypic complexes, considering the mixed compositions of physiological bile acid pools. Experiments performed with synthetic bile acid derivatives showed that iLBPs could act as targets for cell-specific contrast agents and, more generally, as effective carriers of amphiphilic drugs. This review collects the major findings related to bile salt interactions with iLBPs aiming to provide keys for a deeper understanding of protein-mediated intracellular bile salt trafficking.
authors.affiliation: Department of Biotechnology, University of Verona, Strada Le Grazie 15, Verona 37134, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Favretto
authors.affiliation: Department of Biotechnology, University of Verona, Strada Le Grazie 15, Verona 37134, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ceccon
authors.affiliation: Department of Biotechnology, University of Verona, Strada Le Grazie 15, Verona 37134, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Zanzoni
authors.affiliation: Department of Biotechnology, University of Verona, Strada Le Grazie 15, Verona 37134, Italy.
authors.forename: Mariapina
authors.initials: M
authors.lastname: D'Onofrio
authors.affiliation: Institute for Macromolecular Studies, National Research Council, Via Bassini 15, Milan 20133, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ragona
authors.affiliation: Institute for Macromolecular Studies, National Research Council, Via Bassini 15, Milan 20133, Italy.
authors.forename: Henriette
authors.initials: H
authors.lastname: Molinari
authors.affiliation: Department of Biotechnology, University of Verona, Strada Le Grazie 15, Verona 37134, Italy. Electronic address: michael.assfalg@univr.it.
authors.forename: Michael
authors.initials: M
authors.lastname: Assfalg
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D003287:Contrast Media / Q000493:pharmacokinetics; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D013501:Surface-Active Agents / Q000493:pharmacokinetics
chemical_list: D001647:Bile Acids and Salts; D002352:Carrier Proteins; D003287:Contrast Media; D050556:Fatty Acid-Binding Proteins; D008562:Membrane Glycoproteins; D013501:Surface-Active Agents; C037643:bile acid binding proteins
keywords: Bile acid binding protein; Bile salt transport; Intracellular lipid binding protein; NMR spectroscopy