Discovery of Itaconate-Mediated Lysine Acylation

• DOI: 10.1021/jacs.3c02332
• Publication Date: 2023-06-05T04:45:53Z
• Authors: Dongyang Liu; Weidi Xiao; Haoting Li; Yanling Zhang; Shouli Yuan; Chengxi Li; Suwei Dong; Chu Wang
• Keywords: Histones; Lysine; Acylation; Succinates; Protein Processing, Post-Translational; 3. Good health

Itaconate is an important antimicrobial and immunoregulatory metabolite involved in host-pathogen interactions. A key mechanistic action of itaconate through the covalent modification cysteine residues via Michael addition, resulting "itaconation". However, it unclear whether has other regulatory mechanisms. In this work, we discovered a novel type post-translational by promiscuous antibody enrichment data analysis with open-search strategy further confirmed as lysine "itaconylation". We showed that itaconylation its precursor itaconyl-CoA undergo significant upregulation upon lipopolysaccharides (LPS) stimulation RAW264.7 macrophages. Quantitative proteomics identified sites multiple functional proteins, including glycolytic enzymes histones, some which were synthetic peptide standards. The discovery opens up new areas for studying how participates immunoregulation protein modification.