The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.
Trypsin Cleaves Exclusively C-terminal to Arginine and Lysine Residues
Open accessAbstract
Almost all large-scale projects in mass spectrometry-based proteomics use trypsin to convert protein mixtures into more readily analyzable peptide populations. When searching peptide fragmentation spectra against sequence databases, potentially matching peptide sequences can be required to conform to tryptic specificity, namely, cleavage exclusively C-terminal to arginine or lysine. In many published reports, however, significant numbers of proteins are identified by non-tryptic peptides. Here we use the sub-parts per million mass accuracy of a new ion trap Fourier transform mass spectrometer to achieve more than a 100-fold increased confidence in peptide identification compared with typical ion trap experiments and show that trypsin cleaves solely C-terminal to arginine and lysine. We find that non-tryptic peptides occur only as the C-terminal peptides of proteins and as breakup products of fully tryptic peptides N-terminal to an internal proline. Simulating lower mass accuracy led to a large number of proteins erroneously identified with non-tryptic peptide hits. Our results indicate that such peptide hits in previous studies should be re-examined and that peptide identification should be based on strict trypsin specificity.
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Perkins, D. N., Pappin, D. J. C., Creasy, D. M., & Cottrell, J. S. (1999) · Electrophoresis · doi:10.1002/(sici)1522-2683(19991201)20:18<3551::aid-elps3551>3.0.co;2-2 · Cited by 8,203
Mass spectrometry-based proteomics
Aebersold, R., & Mann, M. (2003) · Nature · doi:10.1038/nature01511 · Cited by 6,955
Self-citationA Statistical Model for Identifying Proteins by Tandem Mass Spectrometry
Nesvizhskii, A. I., Keller, A., Kolker, E., & Aebersold, R. (2003) · Analytical Chemistry · doi:10.1021/ac0341261 · Cited by 4,809
Rappsilber, J., Ishihama, Y., & Mann, M. (2003) · Analytical Chemistry · doi:10.1021/ac026117i · Cited by 2,644
Self-citationFourier transform ion cyclotron resonance mass spectrometry: A primer
Marshall, A. G., Hendrickson, C. L., & Jackson, G. S. (1998) · Mass Spectrometry Reviews · doi:10.1002/(sici)1098-2787(1998)17:1<1::aid-mas1>3.0.co;2-k · Cited by 1,990
Femtomole sequencing of proteins from polyacrylamide gels by nano-electrospray mass spectrometry
Wilm, M., Shevchenko, A., Houthaeve, T., Breit, S., Schweigerer, L., Fotsis, T., & Mann, M. (1996) · Nature · doi:10.1038/379466a0 · Cited by 1,680
Self-citationPeng, J., Elias, J. E., Thoreen, C. C., Licklider, L. J., & Gygi, S. P. (2003) · Journal of Proteome Research · doi:10.1021/pr025556v · Cited by 1,647
Error-Tolerant Identification of Peptides in Sequence Databases by Peptide Sequence Tags
Mann, M., & Wilm, M. (1994) · Analytical Chemistry · doi:10.1021/ac00096a002 · Cited by 1,468
Self-citationProteomic characterization of the human centrosome by protein correlation profiling
Andersen, J. S., Wilkinson, C. J., Mayor, T., Mortensen, P., Nigg, E. A., & Mann, M. (2003) · Nature · doi:10.1038/nature02166 · Cited by 1,319
Self-citationProtein sequencing by tandem mass spectrometry.
Hunt, D. F., Yates, J. R., Shabanowitz, J., Winston, S., & Hauer, C. R. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.17.6233 · Cited by 1,180
Cited by
Elias, J. E., & Gygi, S. P. (2007) · Nature Methods · doi:10.1038/nmeth1019 · Cited by 3,925
Mass spectrometry–based proteomics turns quantitative
Ong, S.-E., & Mann, M. (2005) · Nature Chemical Biology · doi:10.1038/nchembio736 · Cited by 1,572
Self-citationDieterich, D. C., Link, A. J., Graumann, J., Tirrell, D. A., & Schuman, E. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601637103 · Cited by 874
Vermeulen, M., Eberl, H. C., Matarese, F., Marks, H., Denissov, S., Butter, F., Lee, K. K., Olsen, J. V., Hyman, A. A., Stunnenberg, H. G., et al. (2010) · Cell · doi:10.1016/j.cell.2010.08.020 · Cited by 806
Self-citationQuantitative mass spectrometry in proteomics: critical review update from 2007 to the present
Bantscheff, M., Lemeer, S., Savitski, M. M., & Kuster, B. (2012) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-012-6203-4 · Cited by 801
Metadata
- Authors
- Olsen, J. V., Ong, S.-E., & Mann, M.
- Venue
- Molecular & Cellular Proteomics
- Publisher
- Elsevier BV
- Published
- 2004-06
- Volume
- 3
- Issue
- 6
- Pages
- 608-614
- ISSN
- 1535-9476 (ISSN-L)
- OpenAlex
- W2141036148
- Cited by
- 1,254
- References
- 20
- FWCI
- 17.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Olsen, J. V., Ong, S.-E., & Mann, M. (2004). Trypsin Cleaves Exclusively C-terminal to Arginine and Lysine Residues. Molecular & Cellular Proteomics. https://doi.org/10.1074/mcp.t400003-mcp200
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