🇬🇧 Revealing protein diversity by mass spectrometry: Post-translational modifications in cell signaling and chromatin biology

Many dynamic biochemical processes in the cell are controlled by proteins. Protein activity and interactions are accurately modulated by regulatory (reversible) chemical modifications of distinct amino acids in proteins, known as post-translational modifications (PTMs). My laboratory develops and applies mass spectrometry technologies to study proteins and their PTMs. I will describe a series of examples from past and current research to demonstrate the capabilities of mass spectrometry to identify and quantify PTMs in complex biological systems. I will focus on protein phosphorylation and on regulatory modifications of histones in chromatin. I will introduce different approaches to PTM-mapping of proteins, covering bottom-up, middle-down and top-down protein analysis strategies for detailed characterization of protein diversity. Recently, ion mobility spectrometry has proven useful for separation of near-identical protein species, as illustrated by detection of different acetylated histone H4 proteoforms generated by the KAT8 acetyltransferase.