Department of Molecular Pharmacology, Institute of Biomolecular Chemistry, Chemical Research Center, Budapest, Pusztaszeri út, Hungary.
Biochem Biophys Res Commun. 2010 Mar 5;393(2):242-7. doi: 10.1016/j.bbrc.2010.01.110. Epub 2010 Feb 1.
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.
首次发现丝氨酸蛋白酶抑制剂家族成员和血浆急性期成分人α1-抗胰蛋白酶（AAT）具有体外伴侣样活性。 光散射实验结果表明，AAT 可有效抑制各种测试蛋白（包括醇脱氢酶、醛缩酶、碳酸酐酶、过氧化氢酶、柠檬酸合酶、烯醇酶、谷胱甘肽 S-转移酶、L-乳酸脱氢酶和β（L）-晶状体蛋白）的热诱导和化学诱导聚集。 结果表明，独特的亚稳态丝氨酸蛋白酶结构能够实现双重功能，即蛋白酶抑制作用和伴侣活性，并强调丝氨酸蛋白酶超家族可能是额外的细胞内和细胞外伴侣（如α1-抗糜蛋白酶）的来源。 鉴于突变形式的 AAT 和其他丝氨酸蛋白酶在称为丝氨酸蛋白酶病的疾病发病机制中的已知作用，这一发现令人惊讶，丝氨酸蛋白酶病的特征是异常构象转变和随后的丝氨酸蛋白酶蛋白自身聚集。
