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.