Comprehensive mass spectrometric investigation strategies of the human methylproteome

Abstract

Protein methylation has been studies for over two decades, mainly in histones but more recently also in non-histone proteins. Despite the great advances in technologies, particularly the application of Orbitrap technology, proteomic analysis of methylation still remains a challenge. This is mainly due to the small size of methylations, their position on fragmented peptides and issue of incorrect identification. A number of different methods have been developed or modified to varying degrees of success in order to enrich for protein methylation prior to mass spectrometric analysis. Despite the availability of different techniques, it is important to understand the underlying strategy employed, the type of sample being analysed and the methylation-related question being investigated. Without such knowledge it is very easy to become lost analysing large volumes of insignificant data or misinterpret the data output.