Lai Shu-Jung, Tu I-Fan, Wu Wan-Ling, Yang Jhih-Tian, Luk Louis Y P, Lai Mei-Chin, Tsai Yu-Hsuan, Wu Shih-Hsiung
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
PhD Program in Microbial Genomics, National Chung Hsing University and Academia Sinica, Taichung, Taiwan.
BMC Microbiol. 2017 May 25;17(1):123. doi: 10.1186/s12866-017-1034-2.
Phosphorylation of amino acid residues on proteins is an important and common post-translational modification in both eukaryotes and prokaryotes. Most research work has been focused on phosphorylation of serine, threonine or tyrosine residues, whereas phosphorylation of other amino acids are significantly less clear due to the controversy on their stability under standard bioanalytical conditions.
Here we applied a shotgun strategy to analyze the histidine and aspartate phosphorylations in different microbes. Our results collectively indicate that histidine and aspartate phosphorylations frequently occur also in proteins that are not part of the two-component systems. Noticeably, a number of the modified proteins are pathogenesis-related or essential for survival in host. These include the zinc ion periplasmic transporter ZnuA in Acinetobacter baumannii SK17, the multidrug and toxic compound extrusion (MATE) channel YeeO in Klebsiella pneumoniae NTUH-K2044, branched amino acid transporter AzlC in Vibrio vulnificus and the RNA-modifying pseudouridine synthase in Helicobacter pylori.
In summary, histidine and aspartate phosphorylation is likely to be ubiquitous and to take place in proteins of various functions. This work also sheds light into how these functionally important proteins and potential drug targets might be regulated at a post-translational level.
蛋白质氨基酸残基的磷酸化是真核生物和原核生物中一种重要且常见的翻译后修饰。大多数研究工作都集中在丝氨酸、苏氨酸或酪氨酸残基的磷酸化上，而由于其他氨基酸在标准生物分析条件下的稳定性存在争议，它们的磷酸化情况则明显不太清楚。
在这里，我们应用鸟枪法策略分析了不同微生物中的组氨酸和天冬氨酸磷酸化。我们的结果共同表明，组氨酸和天冬氨酸磷酸化也经常发生在不属于双组分系统的蛋白质中。值得注意的是，许多被修饰的蛋白质与发病机制相关或对在宿主体内存活至关重要。这些包括鲍曼不动杆菌SK17中的锌离子周质转运蛋白ZnuA、肺炎克雷伯菌NTUH-K2044中的多药和有毒化合物外排（MATE）通道YeeO、创伤弧菌中的支链氨基酸转运蛋白AzlC以及幽门螺杆菌中的RNA修饰假尿苷合酶。
总之，组氨酸和天冬氨酸磷酸化可能普遍存在，并发生在各种功能的蛋白质中。这项工作还揭示了这些功能重要的蛋白质和潜在药物靶点在翻译后水平可能是如何被调控的。
