Inhibition of heat- and chemical-induced aggregation of various proteins reveals chaperone-like activity of the acute-phase component and serine protease inhibitor human alpha(1)-antitrypsin.
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.
Zsila
Ferenc
F
Department of Molecular Pharmacology, Institute of Biomolecular Chemistry, Chemical Research Center, Budapest, Pusztaszeri út, Hungary. zsferi@chemres.hu
D000097:Acetonitriles / Q000494:pharmacology; D000210:Acute-Phase Reaction / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism*
D000097:Acetonitriles; D018832:Molecular Chaperones; D011506:Proteins; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D007770:L-Lactate Dehydrogenase; D002950:Citrate (si)-Synthase; C032159:acetonitrile