Dr. Di Zhang published a paper in Nature Chemical Biology with his collaborators.
Lysine L-lactylation (KL-la) is a novel protein posttranslational modification (PTM) driven by L-lactate. This PTM has three isomers: KL-la, N-ε-(carboxyethyl)-lysine (Kce) and D-lactyl-lysine (KD-la), which are often confused in the context of the Warburg effect and nuclear presence. Here we introduce two methods to differentiate these isomers: a chemical derivatization and high-performance liquid chromatography analysis for efficient separation, and isomer-specific antibodies for high-selectivity identification. We demonstrated that KL-la is the primary lactylation isomer on histones and dynamically regulated by glycolysis, not KD-la or Kce, which are observed when the glyoxalase system was incomplete. The study also reveals that lactyl-coenzyme A, a precursor in L-lactylation, correlates positively with KL-la levels. This work not only provides a methodology for distinguishing other PTM isomers, but also highlights KL-la as the primary responder to glycolysis and the Warburg effect.
Original link: https://www.nature.com/articles/s41589-024-01680-8.
