The role of dynamics in modulating ligand exchange in intracellular lipid binding proteins.
Lipids are essential for many biological processes and crucial in the pathogenesis of several diseases. Intracellular lipid-binding proteins (iLBPs) provide mobile hydrophobic binding sites that allow hydrophobic or amphipathic lipid molecules to penetrate into and across aqueous layers. Thus iLBPs mediate the lipid transport within the cell and participate to a spectrum of tissue-specific pathways involved in lipid homeostasis. Structural studies have shown that iLBPs' binding sites are inaccessible from the bulk, implying that substrate binding should involve a conformational change able to produce a ligand entry portal. Many studies have been reported in the last two decades on iLBPs indicating that their dynamics play a pivotal role in regulating ligand binding and targeted release. The ensemble of reported data has not been reviewed until today. This review is thus intended to summarize and possibly generalize the results up to now described, providing a picture which could help to identify the missing notions necessary to improve our understanding of the role of dynamics in iLBPs' molecular recognition. Such notions would clarify the chemistry of lipid binding to iLBPs and set the basis for the development of new drugs.
Laboratorio NMR, Istituto per lo Studio delle Macromolecole (ISMAC), CNR, Via Bassini 15, 20133 Milano, Italy.
Laura
L
Ragona
Laboratorio NMR, Istituto per lo Studio delle Macromolecole (ISMAC), CNR, Via Bassini 15, 20133 Milano, Italy.
Katiuscia
K
Pagano
Laboratorio NMR, Istituto per lo Studio delle Macromolecole (ISMAC), CNR, Via Bassini 15, 20133 Milano, Italy.
Simona
S
Tomaselli
Dipartimento di Biotecnologie, Università degli Studi di Verona, Strada Le Grazie 15, 37134 Verona, Italy.
Filippo
F
Favretto
Dipartimento di Biotecnologie, Università degli Studi di Verona, Strada Le Grazie 15, 37134 Verona, Italy.
Alberto
A
Ceccon
Dipartimento di Biotecnologie, Università degli Studi di Verona, Strada Le Grazie 15, 37134 Verona, Italy.
Serena
S
Zanzoni
Dipartimento di Biotecnologie, Università degli Studi di Verona, Strada Le Grazie 15, 37134 Verona, Italy.
Mariapina
M
D'Onofrio
Dipartimento di Biotecnologie, Università degli Studi di Verona, Strada Le Grazie 15, 37134 Verona, Italy.
Michael
M
Assfalg
Laboratorio NMR, Istituto per lo Studio delle Macromolecole (ISMAC), CNR, Via Bassini 15, 20133 Milano, Italy. Electronic address: henriette.molinari@univr.it.
Henriette
H
Molinari
D000818:Animals; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000737:chemistry*; D011487:Protein Conformation
D050556:Fatty Acid-Binding Proteins; D008024:Ligands; D008055:Lipids
Intracellular lipid binding protein; Lipid binding; Nuclear magnetic resonance; Protein dynamics