Dataset Information

A Bioorthogonal Chemical Reporter for the Detection and Identification of Protein Lactylation

ABSTRACT: L-Lactylation is a recently discovered post-translational modification occurring on histone lysine residues to regulate gene expression. However, the substrate scope of lactylation, especially that in non-histone proteins, remains unknown, largely due to the limitations of current methods for analyzing lactylated proteins. Herein, we report an alkynyl-functionalized bioorthogonal chemical reporter, YnLac, for the detection and identification of protein lactylation in mammalian cells. Our in-gel fluorescence and chemical proteomic analyses show that YnLac is metabolically incorporated into lactylated proteins and directly labels known lactylated lysines of histones. We further apply YnLac to the proteome-wide profiling of lactylation, revealing many novel modification sites in non-histone proteins for the first time.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Tao Peng

LAB HEAD: Tao Peng

PROVIDER: PXD033454 | Pride | 2022-06-23

REPOSITORIES: Pride

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A bioorthogonal chemical reporter for the detection and identification of protein lactylation.

Sun Yanan Y Chen Yanchi Y Peng Tao T

Chemical science 20220426 20

l-Lactylation is a recently discovered post-translational modification occurring on histone lysine residues to regulate gene expression. However, the substrate scope of lactylation, especially that in non-histone proteins, remains unknown, largely due to the limitations of current methods for analyzing lactylated proteins. Herein, we report an alkynyl-functionalized bioorthogonal chemical reporter, YnLac, for the detection and identification of protein lactylation in mammalian cells. Our in-gel ...[more]

PMID: 35685793

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Project description:Mesenchymal stem cell (MSC) therapy improves liver function in patients with liver cirrhosis. However, the therapeutic mechanism underlying MSC therapy remains unclear. Therefore, this study aimed to elucidate the therapeutic mechanism underlying MSC therapy by analyzing changes in the modification and expression of proteins 1-month post-treatment with MSCs. This prospective study included 11 patients with cirrhosis who received MSC injection in the First Hospital of Lanzhou University. The laboratory indexes before and after treatment were collected to evaluate the clinical treatment effect of MSCs, and peptide segments were extracted from liver tissue before and after treatment to revealed the protein expression and lactylation modification. Meanwhile, weighted gene co-expression network analysis was used to analyze co-expression protein modules and their relationship with clinical features. The patients with liver cirrhosis showed an improvement trend after receiving MSC treatment, specifically, the liver protein synthesis function was significantly improved and coagulation function was also significantly improved. Proteomics combined with lactic acid proteomics revealed 160 Lysine lactylation (Kla) sites of 119 proteins. The downregulated lactylated proteins were associated with metabolic processes. The upregulated lactylated proteins were involved in biological processes. The protein-based co-expression module was significantly related to alkaline phosphatase, total bilirubin (TBIL), indirect bilirubin (IBIL), direct bilirubin (DBIL), and ALB, and 10 proteins significantly related to ALB and 10 proteins significantly related to bilirubin were screened. The changes in clinical indexes before and after treatment indicate that the clinical effects of MSC treatment are related to cell metabolism. Overall, this study is the first study to comprehensively and systematically reveal the changes of lactylated proteins and expression after treatment with MSC by the self-control of patients, and lays a foundation for understanding the functions of lactylation modification in MSC therapy.

Project description:Lysine lactylation (Kla) is a newly discovered histone post-translational modification (PTM), playing important roles in regulating transcription in macrophages. Increasing evidence demonstrates that lysine lactylation plays an important regulatory role in metabolic processes in both bacterial and human cells. However, little is known about the extent and function of lysine lactylation in fungi, here investigated with the black yeast Phialophora verrucosaverrucose as a model organism. WeHere, we report the first proteomic survey of this modification in P. verrucosa. We performed a global lactylation analysis of P. verrucosa using high accuracy bottom-up nano-LC-MS/MS in combination wwith the enrichment of lactylated peptides from digested cell lysates and subsequent peptide identification. In total, 636 lactylation sites on 420 lactylated proteins were identified in this pathogen, of which contained in 26 types of modification motifs. Our results show that over 85% of lactylated proteins were distributed in cytoplasm, mitochondria, and nucleus. The identified proteins were found to be involved associated toin diverse biological processes and were significantly enriched in the melanin biosynthesis process. Most strikingly, Kla was found in 23 structural constituent proteins of ribosome, indicating an impact of Kla in protein synthesis . Moreover, 12 lactylated proteins participated in fungal pathogenicity, suggesting a potential role for Kla in this process. Protein interaction network analysis suggested that a mass of protein interactions are regulated by lactylation. Together, our findings reveal widespread roles for lysine lactylation in regulating metabolism and melanin biosynthesis in P. verrucosa. Our data provide a rich resource for functional analyses of lactylation and facilitate the dissection of metabolic networks in this pathogen. The combined data sets represent the first report of the lactylome of P. verrucosa and provide a good foundation for further explorations of Kla in clinical fungal pathogens.

Dataset Information

A Bioorthogonal Chemical Reporter for the Detection and Identification of Protein Lactylation

Publications

A bioorthogonal chemical reporter for the detection and identification of protein lactylation.

Similar Datasets

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