New Protein Modification Is Uncovered

Proteomics researchers at the University of Chicago have discovered a previously unknown posttranslational modification in proteins. Posttranslational modifications often play an important role in the regulation of cellular processes. Using mass spectrometry, Yingming Zhao and coworkers identified lysine succinylation on the basis of a 100.0186-dalton mass shift in a peptide from isocitrate dehydrogenase, an enzyme that catalyzes a step in the citric acid cycle (Nat. Chem. Biol., DOI: 10.1038/­nchembio.495). They show, through a combination of MS/MS and chromatographic coelution, that the mass shift results from the addition of succinyl rather than methylmalonyl, its isomer. They further verified the succinylation process through a variety of methods, including western blot analysis, an antibody-based method; in vivo labeling with isotopically labeled succinate; and coelution of the corresponding synthetic peptides by liquid chromatography. They found that lysine succinylation is evolutionarily conserved from bacteria to mammalian cells. They have not yet identified the enzyme responsible for modifying the amino acid in vivo or determined the modification’s biological significance.