Functional decorations: post-translational modifications and heart disease delineated by targeted proteomics

The more than 300 currently identified post-translational modifications (PTMs) provides great scope for subtle or dramatic alteration of protein structure and function. Furthermore, the rapid and transient nature of many PTMs allows efficient signal transmission in response to internal and environmental stimuli. PTMs are predominantly added by enzymes, and the enzymes responsible (such as kinases) are thus attractive targets for therapeutic interventions. Modifications can be grouped according to their stability or transience (reversible versus irreversible): irreversible types (such as irreversible redox modifications or protein deamidation) are often associated with aging or tissue injury, whereas transient modifications are associated with signal propagation and regulation. This is particularly important in the setting of heart disease, which comprises a diverse range of acute (such as ischemia/reperfusion), chronic (such as heart failure, dilated cardiomyopathy) and genetic (such as hypertrophic cardiomyopathy) disease states, all of which have been associated with protein PTM. Recently the interplay between diverse PTMs has been suggested to also influence cellular function, with cooperation or competition for sites of modification possible. Here we discuss the utility of proteomics for examining PTMs in the context of the molecular mechanisms of heart disease.