Milk acylation is a new type of post-translation modification in protein, which was reported by Professor Zhao Yingming of the University of Chicago in the journal Nature on 20 19 [2]. Subsequent studies have found that lactic acid modification is an important way for lactic acid to play its role, and it is involved in cell functions related to glycolysis [3], macrophage polarization [4], tumor proliferation regulation [5], nerve cell regulation [6], plant metabolism synthesis [7] and other important life activities. However, the distribution and biological function of protein lactate in early clades are still unclear.
Recently, Professor Chen Qijun's team published a paper in Frontier in Cell and Development Biology entitled "protein Latency Regulates Energy Metabolism in Protozoan Parasite Trypanosoma brucei". In this paper, the metabolic regulation of lactic acid modification in Trypanosoma brucei was reported for the first time, and the relationship between lactose and glycolysis was discussed at different levels. The results laid a foundation for studying the lactic acid action of Trypanosoma brucei, and provided a potential drug intervention target for the prevention and treatment of Trypanosoma brucei. Jingjie Bio provided quantitative analysis of lactic acid modified pan-antibody and lactic acid modified genomics for this study.
Firstly, researchers used lactic acid modified pan-antibody to detect lactic acid protein widely distributed in Trypanosoma brucei by WB technology. Then, 387 L-lysine lactic acid (KLA) loci on 257 lactic acid proteins were identified by using mass spectrometry-based lactic acid modified genomics technology. Protein's functional annotation analysis shows that most lactated proteins are related to metabolic processes, and participate in cellular processes such as protein translation, carbohydrate metabolism, chromatin dynamic regulation, DNA recombination and repair.
Distribution and enrichment analysis of Figure Kla protein
In this study, the Kla loci distributed on histone were further analyzed and compared with the post-translation modification map of trypan protein in previous studies. It is found that 65,438+06 KLA loci are related to other post-translational modifications (PTMs), which means that these PTMs play a dynamic and complex role in regulating histone function. Because Trypanosoma brucei mainly regulates gene expression after transcription, 66 Kla sites were identified on 40 RNA binding proteins (RBPs), most of which were elongation factors, including EF 1α2, which means that lactic acid modification may play a role in gene expression regulation. Trypanosoma brucei lacks TCA cycle, and glycolysis is its main energy metabolism pathway. In this study, 25 Kla sites were identified on 7 glycolytic enzymes, and it was found that lactic acid modification mainly occurred in the catalytic sites of the enzymes, which may be related to the changes of enzyme activity.
Histone and gene regulatory factors are modified by lactic acid.
Because Trypanosoma lacks lactate dehydrogenase (LDH), it is impossible to convert glucose into lactic acid, so this study further explored the regulatory relationship between glycolysis and lactic acid. By comparing the addition of glucose, glucose analogue 2-DG and LDH inhibitor in three different treatment groups, it was found that increasing glucose concentration would reduce lactic acid in trypanosoma, thus reducing lactic acid level. When the protein level is constant, lactic acid and lactic acid levels decrease with the increase of inhibitor concentration. In addition, comparing the lactic acid level of infected host with that of Trypanosoma brucei cultured in vitro, it was found that the lactic acid modification degree of the former was higher than that of the latter, which indicated that lactic acid in protein was also affected by the surrounding environment of parasites, and lactic acid participated in the infection process of Trypanosoma brucei.
Glycolysis and lactation of Trypanosoma donovani
To sum up, this study reported the protein lactic acid modification map of parasitic protozoa for the first time, which proved once again that protein lactic acid modification is a key modification with multiple cell functions, providing new information for the biological function of lysine lactic acid in the cell physiology of parasitic protozoa, and also providing a new direction for the research of potential drug targets for trypanosoma treatment.
Original: https://www.frontiers.org/articles/10.3389/fcell.2021.719720/full.
refer to
1. Zhang Naiwen, et al. The modified landscape of African Trypanosoma protein after translation. Science.
2. Zhang Di et al. Metabolic regulation of histone acylation on on gene expression. Nature.
3. Li, wait for 2020. Glis 1 promotes the induction of pluripotency through the signal cascade of epigenome-metabolomics-epigenome. Natural metabolism.
4. Ricardo Iriza-Carlo et al., 2020. TLR signal adapter BCAP regulates the transformation from inflammation to repair macrophages by promoting histone lactate. PNAS。
5. Jie Yu et al. 202 1. Histone lactate promotes the expression of m6A reading protein YTHDF2 in ocular melanoma, which drives the tumorigenesis. Genome biology.
6.Hideo Hagihara 1 et al. 202 1. Protein lactate induced by nerve excitation. Cell phone report.
7. Meng Xiaoxi et al, 202 1, comprehensive analysis of lysine lactate in rice grains. Journal of agricultural and food chemistry.
8. Zhang Naiwen, etc. Protein lactate plays a key role in regulating energy metabolism in protozoan parasite Trypanosoma brucei. Frontiers of cell and developmental biology.