Quan Shu, Schneider Irmhild, Pan Jonathan, Von Hacht Annekathrin, Bardwell James C A
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan 48109.
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan 48109; Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan 48109.
J Biol Chem. 2007 Sep 28;282(39):28823-28833. doi: 10.1074/jbc.M705291200. Epub 2007 Aug 3.
The CXXC active-site motif of thiol-disulfide oxidoreductases is thought to act as a redox rheostat, the sequence of which determines its reduction potential and functional properties. We tested this idea by selecting for mutants of the CXXC motif in a reducing oxidoreductase (thioredoxin) that complement null mutants of a very oxidizing oxidoreductase, DsbA. We found that altering the CXXC motif affected not only the reduction potential of the protein, but also its ability to function as a disulfide isomerase and also impacted its interaction with folding protein substrates and reoxidants. It is surprising that nearly all of our thioredoxin mutants had increased activity in disulfide isomerization in vitro and in vivo. Our results indicate that the CXXC motif has the remarkable ability to confer a large number of very specific properties on thioredoxin-related proteins.
硫醇-二硫键氧化还原酶的CXXC活性位点基序被认为起到氧化还原变阻器的作用，其序列决定了它的还原电位和功能特性。我们通过在一种还原性氧化还原酶（硫氧还蛋白）中选择CXXC基序的突变体来补充一种强氧化性氧化还原酶DsbA的无效突变体，从而验证了这一想法。我们发现改变CXXC基序不仅影响蛋白质的还原电位，还影响其作为二硫键异构酶的功能，并且还影响其与折叠蛋白底物和再氧化剂的相互作用。令人惊讶的是，几乎所有我们的硫氧还蛋白突变体在体外和体内的二硫键异构化活性都有所增加。我们的结果表明，CXXC基序具有赋予硫氧还蛋白相关蛋白大量非常特定特性的显著能力。
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