|Title||Inhibition of heat- and chemical-induced aggregation of various proteins reveals chaperone-like activity of the acute-phase component and serine protease inhibitor human α1-antitrypsin|
|Publication Type||Journal Article|
|Year of Publication||2010|
|Journal||Biochem Biophys Res Commun|
|Date Published||2010 Mar 5|
|Keywords||Acetonitriles, Acute-Phase Reaction, alpha 1-Antitrypsin, Citrate (si)-Synthase, Hot Temperature, Humans, L-Lactate Dehydrogenase, Molecular Chaperones, Protein Folding, Proteins, Serine Proteinase Inhibitors|
In vitro chaperone-like activity of the serpin family member and plasma acute-phase component human alpha(1)-antitrypsin (AAT) has been shown for the first time. Results of light-scattering experiments demonstrated that AAT efficiently inhibits both heat- and chemical-induced aggregation of various test proteins including alcohol dehydrogenase, aldolase, carbonic anhydrase, catalase, citrate synthase, enolase, glutathione S-transferase, l-lactate dehydrogenase, and beta(L)-crystallin. The results suggest that the unique metastable serpin architecture enables dual function, protease inhibiton as well as chaperone activity and highlight the serpin superfamily as a possible source of additional intra- and extracellular chaperones (e.g. alpha(1)-antichymotrypsin). The present finding is surprising in the light of the well-known role of mutated forms of AAT and other serpins in the pathogenesis of diseases called serpinopathies that featured with aberrant conformational transitions and consequent self-aggregation of serpin proteins.
|Alternate Journal||Biochem. Biophys. Res. Commun.|