Selective Detection and Quantitation of Protein Arginine and Lysine Methylation by nanoLC-MS/MS

摘要

Methylation of arginine and lysine residues in proteins is a post-translational modification (PTM) that is gaining more and more interest since the recent discovery (2004) of antagonists for methyltransferases [1,2]. Arginine and lysine methylation are involved in many biological processes such as gene silencing via histone H3 (K79) or DNA repair mediated by MRE11. However, the regulation of the methylation process is still obscure and exact location of the site(s) of modification remains an analytical challenge. In this study, we have set up generic LC-MS/MS methods to selectively detect and quantify arginine and lysine methylation and have applied this to yeast histone H3 to study the effect of point mutations in the catalytic site of the methyltransferase Dot1 [3].