Identification of lysine lacylation in A. flavus
Ontology highlight
ABSTRACT:
ORGANISM(S): Aspergillus Flavus Nrrl3357
SUBMITTER: 
Shihua Wang
PROVIDER: PXD057413 | iProX | Thu Oct 31 00:00:00 GMT 2024
REPOSITORIES: iProX
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Project description:Lysine lactylation, a new post-translational modification identified on histones of human and mouse cells, stimulates gene transcription from chromatin directly. However, very little is known in the scope and cellular distribution of lactylated proteins. In the present study, we conducted the first proteome-wide survey of lactylated sites in Trypanosoma brucei, a unicellular parasite causing human African sleeping sickness and livestock nagana disease, using LC-MS/MS to identify peptides enriched by immuno-purification with an anti-lactyllysine antibody. Overall, we identified 387 unique lysine lactylated sites in 257 lactylated proteins with diverse cellular localizations and biological functions. Lactylated proteins are involved in a wide variety of cellular functions such as metabolism and gene regulation. Further, we demonstrate that the lactate-derived lactylation in trypanosome is regulated by glucose metabolism. Collectively, our findings provide the first comprehensive view of the lactylome of T. brucei and suggest that lysine lactylation in trypanosomes involves a diverse array of cellular functions.
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Project description:Protein lactylation is a novel post-translational modification (PTM) involved in many important physiological processes such as macrophage polarization, immune regulation and tumour cell growth. However, most studies to date have focused on the function of lactylation on histones, and little is known about the distribution of lactylation on subcellular proteins. Here, we utilized subcellular fractionation methods to perform the global profiling of lactylation in human colon carcinoma HCT116 cells. This approach detected more unique lactylated proteins compared to the standard method when the amount of antibody and cells was equal. In total, 899 lysine lactylation sites were detected on 441 proteins, including 291 newly discovered lactylation sites and 63 newly lactylated proteins reported under the DDA and DIA acquisition modes. Functional enrichment analysis revealed that the majority of these proteins are involved in nucleosome assembly and slicesome function. For each subcellular fraction, the newly discovered lactylated proteins account for 10% to 20%. Notably, XPC not only has four new lactylation modification sites, but also one of which has been shown to be essential for the nucleotide excision repair process. Additionally, one of the newly discovered lactylation sites in scaffold attachment factor B1 (SAFB1) was found to be very important for the negative regulation of transcriptional activity. In conclusion, we describe a novel method that provides for understanding the characterization of subcellular lactylated proteins.
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