Institute of Microbiology, Ernst-Moritz-Arndt-University of Greifswald, Greifswald, Germany.
Antioxid Redox Signal. 2011 Mar 15;14(6):1049-63. doi: 10.1089/ars.2010.3400. Epub 2010 Oct 28.
Cysteine is notable among the universal, proteinogenic amino acids for its facile redox chemistry. Cysteine thiolates are readily modified by reactive oxygen species (ROS), reactive electrophilic species (RES), and reactive nitrogen species (RNS). Although thiol switches are commonly triggered by disulfide bond formation, they can also be controlled by S-thiolation, S-alkylation, or modification by RNS. Thiol-based switches are common in both prokaryotic and eukaryotic organisms and activate functions that detoxify reactive species and restore thiol homeostasis while repressing functions that would be deleterious if expressed under oxidizing conditions. Here, we provide an overview of the best-understood examples of thiol-based redox switches that affect gene expression. Intra- or intermolecular disulfide bond formation serves as a direct regulatory switch for several bacterial transcription factors (OxyR, OhrR/2-Cys, Spx, YodB, CrtJ, and CprK) and indirectly regulates others (the RsrA anti-σ factor and RegB sensory histidine kinase). In eukaryotes, thiol-based switches control the yeast Yap1p transcription factor, the Nrf2/Keap1 electrophile and oxidative stress response, and the Chlamydomonas NAB1 translational repressor. Collectively, these regulators reveal a remarkable range of chemical modifications exploited by Cys residues to effect changes in gene expression.
半胱氨酸是普遍存在的、蛋白质编码的氨基酸中，其氧化还原化学性质非常显著。半胱氨酸硫醇很容易被活性氧（ROS）、活性亲电物质（RES）和活性氮物质（RNS）修饰。虽然硫醇开关通常是由二硫键形成触发的，但它们也可以被 S-硫代化、S-烷基化或 RNS 修饰所控制。基于硫醇的开关在原核和真核生物中都很常见，它们激活了解毒活性物质和恢复硫醇稳态的功能，同时抑制了在氧化条件下表达会有害的功能。在这里，我们概述了影响基因表达的基于硫醇的氧化还原开关的最佳研究实例。分子内或分子间二硫键的形成是几个细菌转录因子（OxyR、OhrR/2-Cys、Spx、YodB、CrtJ 和 CprK）的直接调节开关，并间接调节其他转录因子（RsrA 反σ因子和 RegB 感觉组氨酸激酶）。在真核生物中，基于硫醇的开关控制着酵母 Yap1p 转录因子、Nrf2/Keap1 亲电体和氧化应激反应以及衣藻 NAB1 翻译抑制剂。总的来说，这些调节剂揭示了 Cys 残基用于改变基因表达的一系列显著的化学修饰。
