No Substrate Left behind—Mining of Shotgun Proteomics Datasets Rescues Evidence of Proteolysis by SARS-CoV-2 3CLpro Main Protease
Abstract
:1. Introduction
2. Results
2.1. Non-Terminomics Proteomics Datasets Are an Abundant Source of Protein Termini for Terminomics Research
2.2. Mining of Non-Enriched Datasets Yields High Confidence Substrates of SARS-CoV-2 3CLpro
2.3. Identification of Viral Protein Proteolysis during SARS-CoV-2 Infection in Non-Enriched Datasets
2.4. Identification of Infection-Induced Proteolysis in Non-Enriched Samples
3. Discussion
4. Materials and Methods
4.1. Keyword Searches of PRIDE Archive
4.2. Analysis of PXD026797 (Pablos et al. [9] Pre-Enrichment and TAILS N-Termini Enriched Datasets)
4.3. Filtering of Protein Termini Detected by Analysis of PXD026797
4.4. Analysis of Unenriched (PXD021145) and N-Termini Enriched (PXD021152) (Meyer et al. [13], Datasets)
4.5. Statistical Analysis of TMT-Quantified Datasets
4.6. Data Visualization
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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UniProt Accession | Gene | Cleavage Site (P5–P5′) | Cleavage Site P1′ Position | Terminus Type | N-Terminal Label |
---|---|---|---|---|---|
P50454 | SERPINH1 | RSALQ↓SINEW | 172 | N-term | dimethyl |
Q10567 | AP1B1 | SSKLQ↓SSNIF | 879 | N-term | dimethyl |
Q13428 | TCOF1 | AAALQ↓AKSDE | 1313 | N-term | dimethyl |
P11940 | PABPC1 | VAVLQ↓AHQAK | 616 | C-term | - |
P26038 | MSN | EALLQ↓ASRDQ | 406 | C-term | - |
Q9UQ80 | PA2G4 | KALLQ↓SSASR | 360 | C-term | - |
P36578 | RPL4 | EAQVQ↓ASVVK | 363 | C-term | - |
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Bell, P.A.; Overall, C.M. No Substrate Left behind—Mining of Shotgun Proteomics Datasets Rescues Evidence of Proteolysis by SARS-CoV-2 3CLpro Main Protease. Int. J. Mol. Sci. 2023, 24, 8723. https://doi.org/10.3390/ijms24108723
Bell PA, Overall CM. No Substrate Left behind—Mining of Shotgun Proteomics Datasets Rescues Evidence of Proteolysis by SARS-CoV-2 3CLpro Main Protease. International Journal of Molecular Sciences. 2023; 24(10):8723. https://doi.org/10.3390/ijms24108723
Chicago/Turabian StyleBell, Peter A., and Christopher M. Overall. 2023. "No Substrate Left behind—Mining of Shotgun Proteomics Datasets Rescues Evidence of Proteolysis by SARS-CoV-2 3CLpro Main Protease" International Journal of Molecular Sciences 24, no. 10: 8723. https://doi.org/10.3390/ijms24108723