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oai:figshare.com:article/34044406 2026-10-01T11:15:40Z category_1 category_4 category_8 category_13 category_46 category_64 category_132 portal_63 item_type_3 month_year_10_2026

Cross-Species Profiling of Itaconate-Mediated Modifications by a Universal Probe Bin Ma (219839) Dongyang Liu (2891114) Weidi Xiao (1403551) Chu Wang (62506) Biophysics Biochemistry Microbiology Genetics Immunology Cancer Infectious Diseases positive feedback loop metabolic amplification mechanism covalently modify proteins >- infected macrophages macrophages versus bacteria >- aconitate level comprehensive chemoproteomic profiling findings establish isoc3a universal probe designed sustain itaconate biosynthesis profiling lysine itaconylation profiling cysteine itaconation lysine itaconylation cysteine itaconation universal probe bacteria simultaneously aconitate hydratase species profiling report isoc3a isoc3a captures two types situ </ salmonella </ prokaryotic cells mediated modifications innate immunity host cells dynamic changes dehydration activity covalent targets cis </ also revealed The immunometabolite itaconate can covalently modify proteins through cysteine itaconation and lysine itaconylation. Current bioorthogonal itaconate probes show biased specificity for profiling cysteine itaconation in macrophages versus bacteria and are not compatible with profiling lysine itaconylation at all. Here, we report isoC3A, a universal probe designed for the comprehensive chemoproteomic profiling of these two types of itaconate-mediated modifications in both eukaryotic and prokaryotic cells. <i>In situ</i> profiling of <i>Salmonella</i>-infected macrophages by isoC3A captures the dynamic changes of itaconate-mediated modifications in the proteomes of host cells and bacteria simultaneously. It also revealed that itaconate targets critical cysteine residues on the aconitate hydratase, enhances its dehydration activity to boost the <i>cis</i>-aconitate level, and drives a positive feedback loop to sustain itaconate biosynthesis. Together, these findings establish isoC3A as a universal probe for exploring the covalent targets of itaconate and suggest a metabolic amplification mechanism in innate immunity. 2026-10-01T00:00:00Z Dataset Dataset 10.1021/jacs.6c10764.s004 https://figshare.com/articles/dataset/Cross-Species_Profiling_of_Itaconate-Mediated_Modifications_by_a_Universal_Probe/34044406 CC BY-NC 4.0