Genomics, Proteomics & Bioinformatics | 2019
Intriguing Origins of Protein Lysine Methylation: Influencing Cell Function Through Dynamic Methylation
Abstract
‘‘There is a kink (shoulder) on [the] Lys peak. . .” These words scribed in Richard P. Ambler’s laboratory notebook marked the discovery of protein methylation and a segue into a new field of scientific research [1]. Initially, through ion-exchange chromatography and two-dimensional paper chromatography of the hydrolysate of Salmonella typhimurium flagellin, this ‘‘kink” was interpreted as a ‘‘new amino acid”, the e-Nmethyl-lysine (NML). This discovery, bolstered by a subsequent examination of purified NML, was the first glimpse of protein methylation in living cells [1]. Although this exciting new discovery led to an initial surge in interest, focus on protein methylation quickly waned for a number of decades. By the time protein methylation emerged as a field of interest, research into other post-translational modifications (PTMs) was firmly underway. For example, the discovery of lysine (Lys) methylation predated tyrosine (Tyr) phosphorylation by two decades, following a fortuitous discovery of this new type of protein modification in v-Src associated kinase activity [2]. Following the path of early researchers in the discovery of non-histone protein methylation toward modern discoveries in methyllysine proteomics, this article aimed to unpack the key discoveries which paved the way of further understanding and characterization of the functional impact of this small modification over important cellular processes such as cellular growth signaling and DNA damage response, as well as other cellular pathways in disease pathology.