Substrate specificity of thioredoxins and glutaredoxins - towards a functional classification
Substrate specificity of thioredoxins and glutaredoxins - towards a functional classification
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DOI：
10.1016/j.heliyon.2019.e02943
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发表时间：
2019-12-01
期刊：
影响因子：
4
通讯作者：
Lillig, Christopher Horst
中科院分区：
文献类型：
--
作者：
Gellert, Manuela;Hossain, Md Faruq;Lillig, Christopher Horst
蛋白质巯基的时空还原和氧化是所有生命王国中信号转导的重要机制。硫氧还蛋白（Trx）家族蛋白有效地催化巯基-二硫键交换反应，并且该蛋白因其在巯基开关操作中的重要性而被广泛认识。Trx家族蛋白具有广泛的同时非常独特的底物特异性-这是氧化还原开关的先决条件。尽管多方努力，这种特异性的真正性质仍在辩论中。在这里，我们全面比较各种氧化还原蛋白的分类/聚类从所有领域的生活基于它们的相似性，在氨基酸序列，三级结构，和它们的静电性能。我们将这些相似性与存在的共同相互作用伙伴相关联，这些伙伴在以前的各种研究中被确定，并由蛋白质组学筛选提出。这些分析证实，一级和三级结构的相似性，从而所有常见的分类系统，不相关的蛋白质作为硫醇-二硫化物氧化还原酶的目标特异性。相反，一些例子清楚地表明，静电相似性的重要性，其目标的特异性，独立于他们属于的Trx或谷氧还蛋白亚家族。
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.