Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
Nat Chem Biol. 2023 Apr;19(4):507-517. doi: 10.1038/s41589-022-01244-8. Epub 2023 Feb 2.
Protein S-persulfidation (P-SSH) is recognized as a common posttranslational modification. It occurs under basal conditions and is often observed to be elevated under stress conditions. However, the mechanism(s) by which proteins are persulfidated inside cells have remained unclear. Here we report that 3-mercaptopyruvate sulfur transferase (MPST) engages in direct protein-to-protein transpersulfidation reactions beyond its previously known protein substrates thioredoxin and MOCS3/Uba4, associated with HS generation and transfer RNA thiolation, respectively. We observe that depletion of MPST in human cells lowers overall intracellular protein persulfidation levels and identify a subset of proteins whose persulfidation depends on MPST. The predicted involvement of these proteins in the adaptation to stress responses supports the notion that MPST-dependent protein persulfidation promotes cytoprotective functions. The observation of MPST-independent protein persulfidation suggests that other protein persulfidases remain to be identified.
蛋白质 S-连多硫酸化 (P-SSH) 被认为是一种常见的翻译后修饰。它在基础条件下发生，并且在应激条件下经常观察到升高。然而，细胞内蛋白质被连多硫酸化的机制仍不清楚。在这里，我们报告 3-巯基丙酮酸硫转移酶 (MPST) 除了其先前已知的蛋白质底物硫氧还蛋白和 MOCS3/Uba4 之外，还参与直接的蛋白质-蛋白质交叉连多硫酸化反应，分别与 HS 的产生和转移 RNA 的硫醇化有关。我们观察到，人细胞中 MPST 的耗竭降低了细胞内整体蛋白质连多硫酸化水平，并鉴定出一组蛋白质的连多硫酸化依赖于 MPST。这些蛋白质在适应应激反应中的预测参与支持了这样一种观点，即 MPST 依赖性蛋白质连多硫酸化促进细胞保护功能。观察到 MPST 不依赖的蛋白质连多硫酸化表明，仍有待鉴定其他蛋白质连多硫酸酶。
