Deciphering combinatorial post-translational modifications by top-down mass spectrometry

Post-translational modifications (PTMs) create vast structural and functional diversity of proteins, ultimately modulating protein function and degradation, influencing cellular signaling, and regulating transcription. The combinatorial patterns of PTMs increase the heterogeneity of proteins and further mediates their interactions. Advances in mass spectrometrybased proteomics have resulted in identification of thousands of proteins and allowed characterization of numerous types and sites of PTMs. Examination of intact proteins, termed the top-down approach, offers the potential to map protein sequences and localize multiple PTMs on each protein, providing the most comprehensive cataloging of proteoforms. This review describes some of the dividends of using mass spectrometry to analyze intact proteins and showcases innovative strategies that have enhanced the promise of top-down proteomics for exploring the impact of combinatorial PTMs in unsurpassed detail.

Automated summary

Post-translational modifications (PTMs) create diversity in proteins and affect their function and regulation. Mass spectrometry analysis allows identification and analysis of PTMs, providing a comprehensive catalog of protein forms. The top-down approach enables in-depth exploration of the impact of combinatorial PTMs on proteins.