Gellert Manuela, Hossain Md Faruq, Berens Felix Jacob Ferdinand, Bruhn Lukas Willy, Urbainsky Claudia, Liebscher Volkmar, Lillig Christopher Horst
Institute for Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Germany.
Institute for Mathematics and Informatics, University of Greifswald, Germany.
Heliyon. 2019 Dec 17;5(12):e02943. doi: 10.1016/j.heliyon.2019.e02943. eCollection 2019 Dec.
The spatio-temporal reduction and oxidation of protein thiols is an essential mechanism in signal transduction in all kingdoms of life. Thioredoxin (Trx) family proteins efficiently catalyze thiol-disulfide exchange reactions and the proteins are widely recognized for their importance in the operation of thiol switches. Trx family proteins have a broad and at the same time very distinct substrate specificity - a prerequisite for redox switching. Despite of multiple efforts, the true nature for this specificity is still under debate. Here, we comprehensively compare the classification/clustering of various redoxins from all domains of life based on their similarity in amino acid sequence, tertiary structure, and their electrostatic properties. We correlate these similarities to the existence of common interaction partners, identified in various previous studies and suggested by proteomic screenings. These analyses confirm that primary and tertiary structure similarity, and thereby all common classification systems, do not correlate to the target specificity of the proteins as thiol-disulfide oxidoreductases. Instead, a number of examples clearly demonstrate the importance of electrostatic similarity for their target specificity, independent of their belonging to the Trx or glutaredoxin subfamilies.
蛋白质硫醇的时空还原和氧化是所有生命王国信号转导中的一种基本机制。硫氧还蛋白（Trx）家族蛋白能高效催化硫醇-二硫键交换反应，这些蛋白因其在硫醇开关运作中的重要性而被广泛认可。Trx家族蛋白具有广泛且同时非常独特的底物特异性——这是氧化还原开关的一个先决条件。尽管进行了多项研究，但这种特异性的真正本质仍在争论中。在这里，我们基于来自生命所有领域的各种氧化还原蛋白在氨基酸序列、三级结构及其静电性质方面的相似性，全面比较了它们的分类/聚类情况。我们将这些相似性与先前各种研究中确定并通过蛋白质组学筛选提出的共同相互作用伙伴的存在相关联。这些分析证实，一级和三级结构相似性以及由此产生的所有常见分类系统，与这些蛋白质作为硫醇-二硫键氧化还原酶的靶标特异性并无关联。相反，许多例子清楚地表明，静电相似性对其靶标特异性很重要，而与它们属于Trx还是谷氧还蛋白亚家族无关。
