N-Terminomics Strategies for Protease Substrates Profiling
Proteases play a central role in various biochemical pathways catalyzing and regulating key biological events. Proteases catalyze an irreversible post-translational modification called proteolysis by hydrolyzing peptide bonds in proteins. Given the destructive potential of proteolysis, protease acti...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/26/15/4699 |
| _version_ | 1797525283408969728 |
|---|---|
| author | Mubashir Mintoo Amritangshu Chakravarty Ronak Tilvawala |
| author_facet | Mubashir Mintoo Amritangshu Chakravarty Ronak Tilvawala |
| author_sort | Mubashir Mintoo |
| collection | DOAJ |
| description | Proteases play a central role in various biochemical pathways catalyzing and regulating key biological events. Proteases catalyze an irreversible post-translational modification called proteolysis by hydrolyzing peptide bonds in proteins. Given the destructive potential of proteolysis, protease activity is tightly regulated. Dysregulation of protease activity has been reported in numerous disease conditions, including cancers, neurodegenerative diseases, inflammatory conditions, cardiovascular diseases, and viral infections. The proteolytic profile of a cell, tissue, or organ is governed by protease activation, activity, and substrate specificity. Thus, identifying protease substrates and proteolytic events under physiological conditions can provide crucial information about how the change in protease regulation can alter the cellular proteolytic landscape. In recent years, mass spectrometry-based techniques called N-terminomics have become instrumental in identifying protease substrates from complex biological mixtures. N-terminomics employs the labeling and enrichment of native and neo-N-termini peptides, generated upon proteolysis followed by mass spectrometry analysis allowing protease substrate profiling directly from biological samples. In this review, we provide a brief overview of N-terminomics techniques, focusing on their strengths, weaknesses, limitations, and providing specific examples where they were successfully employed to identify protease substrates in vivo and under physiological conditions. In addition, we explore the current trends in the protease field and the potential for future developments. |
| first_indexed | 2024-03-10T09:10:37Z |
| format | Article |
| id | doaj.art-ea206faef1f14d1a84e54f42658360f8 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T09:10:37Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ea206faef1f14d1a84e54f42658360f82023-11-22T06:02:00ZengMDPI AGMolecules1420-30492021-08-012615469910.3390/molecules26154699N-Terminomics Strategies for Protease Substrates ProfilingMubashir Mintoo0Amritangshu Chakravarty1Ronak Tilvawala2Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USADepartment of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USADepartment of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USAProteases play a central role in various biochemical pathways catalyzing and regulating key biological events. Proteases catalyze an irreversible post-translational modification called proteolysis by hydrolyzing peptide bonds in proteins. Given the destructive potential of proteolysis, protease activity is tightly regulated. Dysregulation of protease activity has been reported in numerous disease conditions, including cancers, neurodegenerative diseases, inflammatory conditions, cardiovascular diseases, and viral infections. The proteolytic profile of a cell, tissue, or organ is governed by protease activation, activity, and substrate specificity. Thus, identifying protease substrates and proteolytic events under physiological conditions can provide crucial information about how the change in protease regulation can alter the cellular proteolytic landscape. In recent years, mass spectrometry-based techniques called N-terminomics have become instrumental in identifying protease substrates from complex biological mixtures. N-terminomics employs the labeling and enrichment of native and neo-N-termini peptides, generated upon proteolysis followed by mass spectrometry analysis allowing protease substrate profiling directly from biological samples. In this review, we provide a brief overview of N-terminomics techniques, focusing on their strengths, weaknesses, limitations, and providing specific examples where they were successfully employed to identify protease substrates in vivo and under physiological conditions. In addition, we explore the current trends in the protease field and the potential for future developments.https://www.mdpi.com/1420-3049/26/15/4699protease substratesN-terminomicsCOFRADICTAILSsubtiligaseCHOPS |
| spellingShingle | Mubashir Mintoo Amritangshu Chakravarty Ronak Tilvawala N-Terminomics Strategies for Protease Substrates Profiling Molecules protease substrates N-terminomics COFRADIC TAILS subtiligase CHOPS |
| title | N-Terminomics Strategies for Protease Substrates Profiling |
| title_full | N-Terminomics Strategies for Protease Substrates Profiling |
| title_fullStr | N-Terminomics Strategies for Protease Substrates Profiling |
| title_full_unstemmed | N-Terminomics Strategies for Protease Substrates Profiling |
| title_short | N-Terminomics Strategies for Protease Substrates Profiling |
| title_sort | n terminomics strategies for protease substrates profiling |
| topic | protease substrates N-terminomics COFRADIC TAILS subtiligase CHOPS |
| url | https://www.mdpi.com/1420-3049/26/15/4699 |
| work_keys_str_mv | AT mubashirmintoo nterminomicsstrategiesforproteasesubstratesprofiling AT amritangshuchakravarty nterminomicsstrategiesforproteasesubstratesprofiling AT ronaktilvawala nterminomicsstrategiesforproteasesubstratesprofiling |