The alternative pathway of glutathione degradation is mediated by a novel protein complex involving three new genes in Saccharomyces cerevisiae
The alternative pathway of glutathione degradation is mediated by a novel protein complex involving three new genes in Saccharomyces cerevisiae
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DOI：
10.1534/genetics.106.066944
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发表时间：
2007-03-01
期刊：
影响因子：
3.3
通讯作者：
Bachhawat, Anand Kumar
中科院分区：
文献类型：
--
作者：
Ganguli, Dwaipayan;Kumar, Chitranshu;Bachhawat, Anand Kumar
谷胱甘肽 (GSH)，即 L-γ-谷氨酰-L-半胱氨酰-甘氨酸，是几乎所有真核细胞中存在的主要低分子量硫醇化合物。 GSH 降解通过γ-谷氨酰循环进行，在所有生物体中，该循环都是由γ-谷氨酰转肽酶的作用启动的。在酿酒酵母中描述了一种新的 GSH 降解途径，需要三个以前未表征的基因的参与。这些基因被命名为 DUG1 (YFR044c)、DUG2 (YBR281c) 和 DUG3 (YNL191w)（谷胱甘肽利用缺陷）。虽然具有正常肽键（如 cys-gly 或 glu-cys-gly）的二肽和三肽仅需要编码属于 M20A 金属水解酶家族的蛋白质的功能性 DUG1 基因的存在，但在二肽、γ-glu-cys 或 GSH 中等不寻常的肽键的存在也需要 DUG2 和 DUG3 基因产物的参与。 DUG2 基因编码具有肽酶结构域和大 WD40 重复区域的蛋白质，而 DUG3 基因编码具有谷氨酰胺酰胺转移酶结构域的蛋白质。发现 Dug1p、Dug2p 和 Dug3p 蛋白通过 Dug1p-Dug2p 和 Dug2p-Dug3p 相互作用形成降解体复合物。提出了一个模型来说明 Dug1p/Dug2p/Dug3p 蛋白作为特定 GSH 降解体复合物的功能。
Glutathione (GSH), L-gamma-glutamyl-L-cysteinyl-glycine, is the major low-molecular-weight thiol compound present in almost all eukaryotic cells. GSH degradation proceeds through the gamma-glutamyl cycle that is initiated, in all organisms, by the action of gamma-glutamyl transpeptidase. A novel pathway for the degradation of GSH that requires the participation of three previously uncharacterized genes is described in the yeast Saccharomyces cerevisiae. These genes have been named DUG1 (YFR044c), DUG2 (YBR281c), and DUG3 (YNL191w) (defective in utilization of glutathione). Although dipeptides and tripeptides with a normal peptide bond such as cys-gly or glu-cys-gly required the presence of only a functional DUG1 gene that encoded a protein belonging to the M20A metallohydrolase family, the presence of an unusual peptide bond such as in the dipeptide, gamma-glu-cys, or in GSH, required the participation of the DUG2 and DUG3 gene products as well. The DUG2 gene encodes a protein with a peptidase domain and a large WD40 repeat region, while the DUG3 gene encoded a protein with a glutamine amidotransferase domain. The Dug1p, Dug2p, and Dug3p proteins were found to form a degradosomal complex through Dug1p-Dug2p and Dug2p-Dug3p interactions. A model is proposed for the functioning of the Dug1p/Dug2p/Dug3p proteins as a specific GSH degradosomal complex.