Combinatorial degradomics: Precision tools to unveil proteolytic processes in biological systems

Area of Science:

• Biochemistry
• Proteomics
• Molecular Biology

Background:

• Protein biological activity is regulated by various mechanisms, including post-translational modifications (PTMs).
• Proteolytic processing is an irreversible PTM that generates distinct protein isoforms, known as proteoforms.
• Proteoform dynamics are increasingly linked to various pathological conditions, making their study a key area in proteome research.

Purpose of the Study:

• To provide an overview of current mass spectrometry (MS)-based degradomics methods.
• To outline the optimal application of these methods for studying protease cleavage events.
• To introduce the concept of combinatorial degradomics for advancing protease research.

Main Methods:

• Mass spectrometry (MS)-based proteomics.
• PTM-specific enrichment workflows.
• MS-based degradomics approaches, including global discovery and targeted degradomics.

Main Results:

• An overview of available MS-based degradomics methods is presented.
• Advantages and disadvantages of selected degradomics approaches are discussed.
• State-of-the-art improvements in degradomics technologies are described.

Conclusions:

• MS-based degradomics is a powerful tool for biomedical protease research.
• Combinatorial degradomics, integrating global and targeted approaches, represents an evolution in the field.
• Understanding proteoform dynamics through advanced degradomics is vital for studying disease mechanisms.