Chaperone-like activity of the acute-phase component human serum alpha 1-acid glycoprotein: inhibition of thermal- and chemical-induced aggregation of various proteins.
In vitro chaperone-like activity of the acute-phase component and plasma drug transporter human alpha(1)-acid glycoprotein (AAG) has been shown for the first time. AAG suppressed thermal aggregation of a variety of unrelated enzymatic (e.g., aldolase, catalase, enolase, carbonic anhydrase) and non-enzymatic proteins (beta-lactoglobulin, ovotransferrin) and it also prevented dithiothreitol induced aggregation of insulin. The anti-aggregation ability of AAG was abolished/reduced upon drug binding suggesting that protein-protein interactions established between the lipocalin beta-barrel fold of AAG and hydrophobic surfaces of the stressed proteins are involved in the chaperone-like activity. The results shed some light on the possible biological function of this enigmatic protein and suggest that besides haptoglobin, clusterin, fibrinogen and alpha(2)-macroglobulin AAG can be considered as a novel member of the extracellular molecular chaperones found in human body fluids.
Zsila
Ferenc
F
Department of Molecular Pharmacology, Institute of Biomolecular Chemistry, Chemical Research Center, H-1025 Budapest, Pusztaszeri út 59-67, Hungary. zsferi@chemres.hu
D000210:Acute-Phase Reaction / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D004229:Dithiothreitol / Q000737:chemistry; D006801:Humans; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D009961:Orosomucoid / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D011485:Protein Binding; D011487:Protein Conformation; D011817:Rabbits; D012542:Scattering, Radiation; D013816:Thermodynamics
D018832:Molecular Chaperones; D009961:Orosomucoid; D004229:Dithiothreitol