The winding path of protein methylation research: milestones and new frontiers.

In 1959, while analysing the bacterial flagellar proteins, Ambler and Rees observed an unknown species of amino acid that they eventually identified as methylated lysine. Over half a century later, protein methylation is known to have a regulatory role in many essential cellular processes that range from gene transcription to signal transduction. However, the road to this now burgeoning research field was obstacle-ridden, not least because of the inconspicuous nature of the methyl mark itself. Here, we chronicle the milestone achievements and discuss the future of protein methylation research.