Department of Molecular Pharmacology, Institute of Biomolecular Chemistry, Chemical Research Center, H-1025 Budapest, Pusztaszeri út 59-67, Hungary.
Bioorg Med Chem Lett. 2010 Feb 1;20(3):1205-9. doi: 10.1016/j.bmcl.2009.11.132. Epub 2009 Dec 4.
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.
首次发现急性反应期蛋白和血浆药物转运蛋白人α1-酸性糖蛋白（AAG）具有分子伴侣样活性。AAG 抑制了多种无相关性酶（如醛缩酶、过氧化氢酶、烯醇酶、碳酸酐酶）和非酶蛋白（β-乳球蛋白、卵转铁蛋白）的热聚集，还能防止二硫苏糖醇诱导的胰岛素聚集。药物结合后，AAG 的抗聚集能力被消除/降低，这表明 AAG 的亲脂性结合β桶结构域与应激蛋白的疏水面之间建立的蛋白-蛋白相互作用与分子伴侣样活性有关。该结果揭示了这种神秘蛋白可能的生物学功能，并提示除触珠蛋白、聚集素、纤维蛋白原和α2-巨球蛋白外，AAG 也可被视为人体体液中发现的细胞外分子伴侣的新成员。
