Zhu Siyu, Liu Feng, Wang Hao, Zhang Yongqian
School of Medical Technology, Beijing Institute of Technology, No. 5 Zhongguancun South Street, Beijing 100081, China.
Proteomes. 2025 May 23;13(2):19. doi: 10.3390/proteomes13020019.
, renowned for its exceptional resistance to radiation, provides a robust model for elucidating cellular stress responses and DNA repair mechanisms. Previous studies have established PprI as a key regulator contributing to radiation resistance through its involvement in DNA damage repair pathways, oxidative stress response, and metabolic regulation.
Building upon these foundations, our study employs label-free quantitative (LFQ) proteomics coupled with high-resolution mass spectrometry to systematically map deletion protein networks by comparing the global proteomic profiles of knockout and wild-type strains.
Under stringent screening criteria, we identified 719 significantly higher and 281 significantly lower abundant proteins in the knockout strain compared to wild-type strains. Functional analysis revealed that PprI deficiency disrupts homologous recombination (HR) repair, activates nucleotide excision repair (NER) and base excision repair (BER) as a compensatory mechanism, and impairs Mn/Fe homeostasis and carotenoid biosynthesis, leading to increased oxidative stress. Furthermore, PprI deficiency induces significant metabolic reprogramming, including impaired purine synthesis, compromised cell wall integrity, etc. Conclusions: These proteomic findings delineate the extensive regulatory network influenced by PprI, revealing coordinated perturbations across multiple stress response systems when PprI is absent.
因其对辐射具有卓越抗性而闻名，为阐明细胞应激反应和DNA修复机制提供了一个强大的模型。先前的研究已确定PprI是一种关键调节因子，通过参与DNA损伤修复途径、氧化应激反应和代谢调节，对辐射抗性起到促进作用。
基于这些基础，我们的研究采用无标记定量（LFQ）蛋白质组学结合高分辨率质谱，通过比较敲除和野生型菌株的整体蛋白质组谱，系统地绘制缺失蛋白质网络。
在严格的筛选标准下，我们发现与野生型菌株相比，敲除菌株中有719种蛋白质丰度显著更高，281种蛋白质丰度显著更低。功能分析表明，PprI缺失会破坏同源重组（HR）修复，激活核苷酸切除修复（NER）和碱基切除修复（BER）作为补偿机制，并损害锰/铁稳态和类胡萝卜素生物合成，导致氧化应激增加。此外，PprI缺失会诱导显著的代谢重编程，包括嘌呤合成受损、细胞壁完整性受损等。结论：这些蛋白质组学研究结果描绘了受PprI影响的广泛调控网络，揭示了PprI缺失时多个应激反应系统的协同扰动。
