tailieunhanh - Báo cáo khoa học: Disulfide bridge regulates ligand-binding site selectivity in liver bile acid-binding proteins

Bile acid-binding proteins (BABPs) are cytosolic lipid chaperones that play central roles in driving bile flow, as well as in the adaptation to various pathological conditions, contributing to the maintenance of bile acid homeostasis and functional distribution within the cell. | ỊFEBS Journal Disulfide bridge regulates ligand-binding site selectivity in liver bile acid-binding proteins Clelia Cogliati1 Simona Tomaselli1 Michael Assfalg2 Massimo Pedo2 Pasquale Ferranti3 Lucia Zetta1 Henriette Molinari2 and Laura Ragona1 1 Laboratorio NMR Istituto per lo Studio delle Macromolecole CNR Milan Italy 2 Dipartimento di Biotecnologie Universita di Verona Strada le Grazie Verona Italy 3 Dipartimento di Scienza degli Alimenti University di Napoli Federico II Portici Italy Keywords backbone dynamics disulfide bridge intracellular lipid-binding protein molecular recognition NMR Correspondence L. Ragona Lab. NMR Istituto per lo Studio delle Macromolecole CNR Via Bassini 15 20133 Milano Italy Fax 39 02 23699620 Tel 39 02 23699619 E-mail H. Molinari Dipartimento di Biotecnologie Universita degli Studi di Verona Strada le Grazie 15 37134 Verona Italy Fax 39 0458027929 Tel 39 0458027901 E-mail Received 3 July 2009 revised 17 August 2009 accepted 18 August 2009 doi Bile acid-binding proteins BABPs are cytosolic lipid chaperones that play central roles in driving bile flow as well as in the adaptation to various pathological conditions contributing to the maintenance of bile acid homeostasis and functional distribution within the cell. Understanding the mode of binding of bile acids with their cytoplasmic transporters is a key issue in providing a model for the mechanism of their transfer from the cytoplasm to the nucleus for delivery to nuclear receptors. A number of factors have been shown to modulate bile salt selectivity stoichiometry and affinity of binding to BABPs . chemistry of the ligand protein plasticity and possibly the formation of disulfide bridges. Here the effects of the presence of a naturally occurring disulfide bridge on liver BABP ligand-binding properties and backbone dynamics have been investigated by NMR. Interestingly the disulfide bridge does .