Department of Microbiology, Cornell University, Ithaca, NY, 14853, USA.
Redox Biol. 2021 Jun;42:101935. doi: 10.1016/j.redox.2021.101935. Epub 2021 Mar 6.
The bacterial cytosol is generally a reducing environment with protein cysteine residues maintained in their thiol form. The low molecular weight thiol bacillithiol (BSH) serves as a general thiol reductant, analogous to glutathione, in a wide range of bacterial species. Proteins modified by disulfide bond formation with BSH (S-bacillithiolation) are reduced by the action of bacilliredoxins, BrxA and BrxB. Here, the YtxJ protein is identified as a monothiol bacilliredoxin, renamed BrxC, and is implicated in BSH removal from oxidized cytosolic proteins, including the glyceraldehyde 3-phosphate dehydrogenases GapA and GapB. BrxC can also debacillithiolate the mixed disulfide form of the bacilliredoxin BrxB. Bdr is a thioredoxin reductase-like flavoprotein with bacillithiol-disulfide (BSSB) reductase activity. Here, Bdr is shown to additionally function as a bacilliredoxin reductase. Bdr and BrxB function cooperatively to debacillithiolate OhrR, a transcription factor regulated by S-bacillithiolation on its sole cysteine residue. Collectively, these results expand our understanding of the BSH redox network comprised of three bacilliredoxins and a BSSB reductase that serve to counter the widespread protein S-bacillithiolation that results from conditions of disulfide stress.
细菌胞质通常是一个还原环境，其中蛋白质半胱氨酸残基保持巯基形式。低分子量巯基硫氧还蛋白（BSH）作为一种广泛存在于多种细菌中的通用巯基还原剂，类似于谷胱甘肽。与 BSH 形成二硫键修饰的蛋白质（S-硫氧还蛋白化）通过 bacilliredoxins（BrxA 和 BrxB）的作用被还原。在这里，YtxJ 蛋白被鉴定为单巯基 bacilliredoxin，更名为 BrxC，并涉及 BSH 从氧化的胞质蛋白中去除，包括甘油醛 3-磷酸脱氢酶 GapA 和 GapB。BrxC 还可以去硫氧还蛋白化 bacilliredoxin BrxB 的混合二硫键形式。Bdr 是一种具有 bacillithiol-disulfide（BSSB）还原酶活性的硫氧还蛋白还原酶样黄素蛋白。在这里，显示 Bdr 还具有 bacilliredoxin 还原酶的功能。Bdr 和 BrxB 协同作用，去硫氧还蛋白化 OhrR，这是一种转录因子，其唯一的半胱氨酸残基上的 S-硫氧还蛋白化受到调节。总的来说，这些结果扩展了我们对 BSH 氧化还原网络的理解，该网络由三种 bacilliredoxins 和一种 BSSB 还原酶组成，用于对抗由于二硫键应激而导致的广泛的蛋白质 S-硫氧还蛋白化。
