Abstract
Post translational modifications (PTMs) are covalent modifications of proteins that can range from small chemical modifications to addition of entire proteins. PTMs contribute to regulation of protein function and thereby greatly increase the functional diversity of the proteome. In the heart, a few well-studied PTMs, such as phosphorylation and glycosylation, are known to play essential roles for cardiac function. Yet, only a fraction of the ~ 300 known PTMs have been studied in a cardiac context. Here we investigated the proteome-wide map of PTMs present in human hearts by utilizing high-resolution mass spectrometry measurements and a suite of PTM identification algorithms. Our approach led to identification of more than 150 different PTMs across three of the chambers in human hearts. This finding underscores that decoration of cardiac proteins by PTMs is much more diverse than hitherto appreciated and provides insights in cardiac protein PTMs not yet studied. The results presented serve as a catalogue of which PTMs are present in human hearts and outlines the particular protein and the specific amino acid modified, and thereby provides a detail-rich resource for exploring protein modifications in human hearts beyond the most studied PTMs.
Highlights
Post translational modifications (PTMs) are covalent modifications of proteins that can range from small chemical modifications to addition of entire proteins
Applying a false-discovery rate (FDR) of 0.05 we identified thousands of peaks covering approximately 150 different post translational modifications, which were distributed across approximately 60% of the peptides in the human heart samples
To fully understand the molecular mechanisms contributing to cardiac regulation, we need to expand our knowledge of post translational modifications affecting protein function in the heart
Summary
Post translational modifications (PTMs) are covalent modifications of proteins that can range from small chemical modifications to addition of entire proteins. A critical component of the analysis of shotgun proteomics datasets is the search engine, which is an algorithm that attempts to identify the peptide sequence corresponding to the measured mass to charge ratios by matching the information in acquired spectra with insilico generated information from a protein d atabase[10]. A number of computational methods have been developed aiming at identifying unidentified spectra These methods count tools as Comet-PTM11, MSfragger[12] and P TMselect[13], which are broadly known as ‘open searches’ or ‘error tolerant’ search algorithms. The strategy of these approaches are to use precursor mass. The open search algorithms have been utilized to identify involvement of previously unknown PTMs in d iseases[11,12,15]
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