Li Hui, Wei Jiang-Chun
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Sci Rep. 2016 Jun 2;6:27184. doi: 10.1038/srep27184.
Endocarpon pusillum is a lichen-forming fungus with an outstanding stress resistance property closely related to its antioxidant system. In this study, thioredoxin (Trx), one of the main components of antioxidant defense systems in E. pusillum (EpTrx), was characterized and analyzed both in transgenic yeasts and in vitro. Our analyses identified that the heterologous expression of EpTrx in the yeast Pichia pastoris significantly enhanced its resistance to osmotic and oxidative stresses. Assays in vitro showed EpTrx acted as a disulfide reductase as well as a molecular chaperone by assembling into various polymeric structures. Upon exposure to heat-shock stress, EpTrx exhibited weaker disulfide reductase activity but stronger chaperone activity, which coincided with the switching of the protein complexes from low molecular weight forms to high molecular weight complexes. Specifically, we found that Cys31 near but not at the active site was crucial in promoting the structural and functional transitions, most likely by accelerating the formation of intermolecular disulfide bond. Transgenic Saccharomyces cerevisiae harboring the native EpTrx exhibited stronger tolerance to oxidative, osmotic and high temperature stresses than the corresponding yeast strain containing the mutant EpTrx (C31S). Our results provide the first molecular evidence on how Trx influences stress response in lichen-forming fungi.
微小内丝藻是一种形成地衣的真菌,具有出色的抗逆性,这与其抗氧化系统密切相关。在本研究中,微小内丝藻抗氧化防御系统的主要成分之一硫氧还蛋白(Trx,即EpTrx)在转基因酵母和体外进行了表征和分析。我们的分析表明,EpTrx在毕赤酵母中的异源表达显著增强了其对渗透胁迫和氧化胁迫的抗性。体外实验表明,EpTrx通过组装成各种聚合物结构,既作为二硫键还原酶,又作为分子伴侣发挥作用。在热激胁迫下,EpTrx表现出较弱的二硫键还原酶活性,但具有较强的伴侣活性,这与蛋白质复合物从低分子量形式转变为高分子量复合物相一致。具体而言,我们发现活性位点附近而非活性位点上的Cys31在促进结构和功能转变方面至关重要,最有可能是通过加速分子间二硫键的形成。携带天然EpTrx的转基因酿酒酵母比含有突变型EpTrx(C31S)的相应酵母菌株对氧化、渗透和高温胁迫表现出更强的耐受性。我们的结果首次提供了关于Trx如何影响形成地衣真菌应激反应的分子证据。