Systems-wide proteomic characterization of combinatorial post-translational modification patterns

Abstract

Protein post-translational modifications (PTMs) have been widely shown to influence protein–protein interactions, direct subcellular location and transduce a variety of both internal and externally generated signals into cellular/phenotypic outcomes. Mass spectrometry has been a key tool for the elucidation of several types of PTMs in both qualitative and quantitative manners. As large datasets on the proteome-wide level are now being generated on a daily basis, the identification of combinatorial PTM patterns has become feasible. A survey of the recent literature in this area shows that many proteins undergo multiple modifications and that sequential or hierarchal patterns exist on many proteins; the biology of these modification patterns is only starting to be unraveled. This review will outline combinatorial PTM examples in biology, and the mass spectrometry-based techniques and applications utilized in the investigations of these combinatorial PTMs.

Keywords::

• electron-capture dissociation
• electron-transfer dissociation
• histone code
• mass spectrometry
• middle-down approach
• post-translational modification
• proteomics
• top-down approach

Financial & competing interests disclosure

Benjamin A Garcia acknowledges financial support from the American Society for Mass Spectrometry Research award sponsored by the Waters Corporation, a New Jersey Commission on Cancer Research SEED grant, Princeton University and the National Science Foundation (CBET-0941143). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.