Potential role of glutathione in evolution of thiol-based redox signaling sites in proteins.
Potential role of glutathione in evolution of thiol-based redox signaling sites in proteins.
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DOI：
10.3389/fphar.2015.00001
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发表时间：
2015
影响因子：
5.6
通讯作者：
Wouters MA
中科院分区：
文献类型：
--
作者：
Mohanasundaram KA;Haworth NL;Grover MP;Crowley TM;Goscinski A;Wouters MA
半胱氨酸容易受到活性氧和氮氧化物物种的各种修饰，包括谷胱甘肽基化；当涉及两个半胱氨酸时，形成二硫键。谷氧还蛋白可以将谷胱甘肽-半胱氨酸加合物从蛋白质中去除，而硫氧还蛋白可以还原二硫化物。谷氧还蛋白与二硫键还原硫氧还蛋白同源，具有与蛋白质底物相似的结合方式。这些系统的演变没有得到很好的描述。当蛋白质中存在单个半胱氨酸时，氧化还原缓冲液谷胱甘肽的结合可能会引起构象变化，导致简单的氧化还原开关，从而影响信号级联反应。如果在序列中引入第二个半胱氨酸，则存在形成二硫键的可能性。在有利的蛋白质环境中，可以形成双稳态的氧化还原开关。由于谷氧还蛋白与硫氧还蛋白的相似之处，当添加第二个半胱氨酸时，突变的蛋白质可能立即被挤出到硫氧还蛋白依赖的氧化还原循环中。在这里，我们搜索氧化还原活性半胱氨酸残基的数量在整个进化过程中发生变化的蛋白质底物的例子。我们关注的是跨链二硫化物(CSD)，这是最常见的禁用二硫化物类型。我们搜索了CSD存在、不存在的蛋白质，并且在蛋白质同源基因中也发现了单一的半胱氨酸。选择了三种不同的蛋白质进行详细研究--CD4、ERO1和AKT。我们创建了系统发育树，检查CSD残基在蛋白质进化过程中何时发生突变。我们推测，原始的半胱氨酸很可能是经历硫氧还蛋白亲核攻击的CSD的半胱氨酸。因此，通过将天然序列中的两个残基逐步突变为半胱氨酸，可以将具有氧化还原活性的二硫键引入蛋白质结构。推而广之，蛋白质中结构二硫化物的进化获得可能通过氧化还原活性二硫键状态的转变而发生。
Cysteine is susceptible to a variety of modifications by reactive oxygen and nitrogen oxide species, including glutathionylation; and when two cysteines are involved, disulfide formation. Glutathione-cysteine adducts may be removed from proteins by glutaredoxin, whereas disulfides may be reduced by thioredoxin. Glutaredoxin is homologous to the disulfide-reducing thioredoxin and shares similar binding modes of the protein substrate. The evolution of these systems is not well characterized. When a single Cys is present in a protein, conjugation of the redox buffer glutathione may induce conformational changes, resulting in a simple redox switch that effects a signaling cascade. If a second cysteine is introduced into the sequence, the potential for disulfide formation exists. In favorable protein contexts, a bistable redox switch may be formed. Because of glutaredoxin's similarities to thioredoxin, the mutated protein may be immediately exapted into the thioredoxin-dependent redox cycle upon addition of the second cysteine. Here we searched for examples of protein substrates where the number of redox-active cysteine residues has changed throughout evolution. We focused on cross-strand disulfides (CSDs), the most common type of forbidden disulfide. We searched for proteins where the CSD is present, absent and also found as a single cysteine in protein orthologs. Three different proteins were selected for detailed study—CD4, ERO1, and AKT. We created phylogenetic trees, examining when the CSD residues were mutated during protein evolution. We posit that the primordial cysteine is likely to be the cysteine of the CSD which undergoes nucleophilic attack by thioredoxin. Thus, a redox-active disulfide may be introduced into a protein structure by stepwise mutation of two residues in the native sequence to Cys. By extension, evolutionary acquisition of structural disulfides in proteins can potentially occur via transition through a redox-active disulfide state.
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影响因子：
2.9
作者：
Copley, SD;Novak, WRP;Babbitt, PC
通讯作者：
Babbitt, PC
影响因子：
4.8
作者：
Gallina, A;Hanley, TM;Ryser, HJP
通讯作者：
Ryser, HJP
影响因子：
4.8
作者：
Hansen, Henning Gram;Schmidt, Jonas Damgard;Ellgaard, Lars
通讯作者：
Ellgaard, Lars
DOI：
10.1093/protein/12.7.563
发表时间：
1999-07-01
期刊：
PROTEIN ENGINEERING
影响因子：
--
作者：
Halaby, DM;Poupon, A;Mornon, JP
通讯作者：
Mornon, JP
影响因子：
2.9
作者：
ANIKSZTEJN, L;CHARTON, G;BENARI, Y
通讯作者：
BENARI, Y