Abstract
Peptide mass fingerprinting (PMF) grew from a need for a faster, more efficient method to identify frequently observed proteins in electrophoresis gels. We describe the genesis of the idea in 1989, and show the first demonstration with fast atom bombardment mass spectrometry. Despite its promise, the method was seldom used until 1992, with the coming of significantly more sensitive commercial instrumentation based on MALDI-TOF-MS. We recount the evolution of the method and its dependence on a number of technical breakthroughs, both in mass spectrometry and in other areas. We show how it laid the foundation for high-throughput, high-sensitivity methods of protein analysis, now known as proteomics. We conclude with recommendations for further improvements, and speculation of the role of PMF in the future.
Article PDF
Similar content being viewed by others
References
Matsudaira, P. Sequence from Picomole Quantities of Proteins Electroblotted onto Polyvinylidene Difluoride Membranes. J. Biol. Chem. 1987, 262, 10035–10038.
Orcutt, B. C.; George, D. G.; Dayhoff, M. O. Protein and Nucleic Acid Sequence Database Systems. Annu. Rev. Biophys. Bioeng. 1983, 12, 419–441.
Barber, M.; Bordoli, R. S.; Sedgewick, R. D.; Tyler, A. N. Fast Atom Bombardment of Solids (FAB). A New Ion Source for Mass spectrometry. J. Chem Soc. Chem. Commun. 1981, 11, 325–347.
Torgerson, D. F.; Skowronski, R. P.; Macfarlane, R. D. New Approach to the Mass Spectroscopy of Non-Volatile Compounds. Biochem. Biosphys. Res. Commun. 1974, 60, 616–621.
Henzel, W. J.; Stults, J. T.; Watanabe, C. Proceedings of the Third Symposium of the Protein Society; Seattle, WA, 1989
Cleveland, D. W.; Fischer, S. G.; Kirschner, M. W.; Laemmli, U. K. Peptide Mapping by Limited Proteolysis in Sodium Dodecyl Sulfate and Analysis by Gel Electrophoresis. J. Biol. Chem. 1977, 252, 1102–1106.
Henzel, W. J.; Stults, J. T.; Wong, S. C.; Namenuk, A.; Yashio, J.; Watanabe, C. In Techniques in Protein Chemistry; Marshak, D. R., Ed.; Academic Press: San Diego, 1995; Vol. VII, pp 341–346.
Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Electrospray Ionization for Mass Spectrometry of Large Biomolecule. Science 1989, 246, 64–67.
Karas, M.; Hillenkamp, F. Laser Desorption Ionization of Proteins with Molecular Masses Exceeding 10,000 Daltons. Anal. Chem. 1988, 60, 2299–2301.
Tanaka, K.; Waki, H.; Ido, Y.; Akita, S.; Yoshida, Y.; Yoshida, T. Protein and Polymer Analyses up to m/z 100,000 by Laser Ionization Time-of-flight Mass Spectrometry. Rapid Commun. Mass Spectrom. 1988, 2, 151–153.
Billeci, T. M.; Stults, J. T. Tryptic Mapping of Recombinant Proteins by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry. Anal. Chem. 1993, 65, 1709–1716.
Henzel, W. J.; Billeci, T. M.; Stults, J. T.; Wong, S. C.; Grimley, C.; Watanabe, C. Identifying Proteins from Two-Dimensional Gels by Molecular Mass Searching of Peptide Fragments in Protein Sequence Databases. Proceedings of the National Academy of Sciences; 1993, 90, 5011–5015.
Aebersold, R.; Leavitt, J.; Saavedra, R. A.; Hood, L. E.; Kent, S. B. Internal Amino Acid Sequence Analysis of Proteins Separated by One- or Two-Dimensional Gel Electrophoresis After in Situ Protease Digestion on Nitrocellulose. Proceedings of the National Academy of Sciences; 1987, 84, 6970–6974.
Wong, S. C.; Grimley, C.; Padua, A.; Bourell, J. H.; Henzel, W. J. In Techniques in Protein Chemistry IV; Angeletti, R. H., Ed.; Academic Press: San Diego, 1993, pp 371–378.
Mann, M.; Hojrup, P.; Roepstorff, P. Use of Mass Spectrometric Molecular Weight Information to Identify Proteins in Sequence Databases. Biol. Mass Spectrom. 1993, 22, 338–345.
Pappin, D. J. C.; Hojrup, P.; Bleasby, A. J. Rapid Identification of Proteins by Peptide Mass Fingerprinting. Current Biol. 1993, 3, 327–332.
James, P.; Quadroni, M.; Carafoli, E.; Gonnet, G. Protein identification by Mass Profile Fingerprinting. Biochem. Biophys. Res. Commun. 1993, 195, 58–64.
Yates, J. R., III; Speicher, S.; Griffin, P. R.; Hunkapiller, T. Peptide Mass Maps: A Highly Informative Approach to Protein Identification. Anal. Biochem. 1993, 214, 397–408.
Henzel, W. J.; Grimley, C.; Bourell, J. H.; Billeci, T. M.; Wong, S. C.; Stults, J. T. Analysis of Two-Dimensional Gel Proteins by Mass Spectrometry and Microsequencing. Methods Enzymol. 1994, 6, 239–247.
Mann, M.; Wilm, M. Error-Tolerant Identification of Peptides in Sequence Databases by Peptide Sequence Tags. Anal. Chem. 1994, 66, 4390–4399.
Eng, J. K.; McCormack, A. L.; Yates, J. R. An Approach to Correlate Tandem Mass Spectral Data of Peptides with Amino Acid Sequences in a Protein Database. J. Am. Soc. Mass Spectrom. 1994, 5, 976–989.
Wolters, D. A.; Washburn, M. P.; Yates, J. R. An Automated Multidimensional Protein Identification Technology for Shotgun Proteomics. Anal. Chem. 2001, 73, 5683–5690.
Jungblut, P.; Thiede, B.; Zimny-Arndt, U.; Müller, E. C.; Scheler, C.; Wittmann-Liebold, B.; Otto, A. Resolution Power of Two-Dimensional Electrophoresis and Identification of Proteins from Gels. Electrophoresis 1996, 17, 839–847.
Taylor, J.; Anderson, N. L.; Scandora, A. E., Jr.; Willard, K. E.; Anderson, N. G. Design and Implementation of a Prototype Human Protein Index. Clin. Chem. 1982, 28, 861–866.
Wilkins, M. R.; Sanchez, J.-C.; Gooley, A. A.; Appel, R. D.; Humphrey-Smith, I.; Hochstrasser, D. F.; Williams, K. L. Progress with Proteome Projects: Why All Proteins Expressed by a Genome Should be Identified and How to Do It. Biotech. Gen. Eng. Rev. 1995, 13, 19–50.
Arnott, D.; O’Connell, K. L.; King, K. L.; Stults, J. T. An Integrated Approach to Proteome Analysis: Identification of Proteins Associated with Cardiac Hypertrophy. Anal. Biochem. 1998, 258, 1–18.
Fraser, C. M.; Gocayne, J. D.; White, O.; Adams, M. D.; Clayton, R. A.; Fleischmann, R. D.; Bult, C. J.; Kerlavage, A. R.; Sutton, G. G.; Kelley, J. M.; Fritchman, J. L.; Weidman, J. F.; Small, K. V.; Sandusky, M.; Fuhrmann, J. L.; Nguyen, D. T.; Utterback, T.; Saudek, D. M.; Philips, C. A.; Merrick, J. M.; Tomb, J.; Dougherty, B. A.; Bott, K. F.; Hu, P. C.; Lucier, T. S.; Paterson, S. N.; Smith, H. O.; Venter, J. C. The Minimal Gene Complement of Mycoplasma genitalium. Science 1995, 270, 397–404.
Blattner, F. R.; Plunkett, G.; III, Bloch, C. A.; Perna, N. T.; Burland, V.; Riley, M.; Collado-Vides, J.; Glasner, J. D.; Rode, C. K.; Mayhew, G. F.; Gregor, J.; Davis, N. W.; Kirkpatrick, H. A.; Goeden, M. A.; Rose, D. J.; Mau, B.; Shao, Y. The Complete Genome Sequence of Escherichia coli K-12. Science 1997, 277, 1453–1462.
Yates, J. R., III; Eng, J. K.; McCormack, A. L. Mining Genomes: Correlating Tandem Mass Spectra of Modified and Unmodified Peptides to Sequences in Nucleotide Databases. Anal. Chem. 1995, 67, 3202–3210.
Shevchenko, A.; Jensen, O. N.; Podtelejnikov, A. V.; Sagliocco, F.; Wilm, M.; Vorm, O.; Mortensen, P.; Boucherie, H.; Mann, M. Linking Genome and Proteome by Mass Spectrometry: Large-Scale Identification of Yeast Proteins from Two-Dimensional Gels. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 14440–14445.
Shevchenko, A.; Wilm, M.; Vorm, O.; Mann, M. Mass Spectrometric Sequencing of Proteins from Silver Stained Polyacrylamide Gels. Anal. Chem. 1996, 68, 850–858.
Otto, A.; Thiede, B.; Müller, E. C.; Scheler, C.; Wittmann-Liebold, B.; Jungblut, P. Identification of Human Myocardial Proteins Separated by Two-Dimensional Electrophoresis Using an Effective Sample Preparation for Mass Spectrometry. Electrophoresis 1996, 17, 1643–1650.
Erdjument-Bromage, H.; Lui, M.; Lacomis, L.; Grewal, A.; Annan, R.; McNulty, D.; Carr, S.; Tempst, P. Examination of Micro-Tip Reversed-Phase Liquid Chromatographic Extraction of Peptide Pools for Mass Spectrometry Analysis. J. Chromatogr. A 1998, 826, 167–181.
Gobom, J.; Nordhoff, E.; Mirgorodskaya, E.; Ekman, R.; Roepstorff, P. Sample Purification and Preparation Technique Based on Nano-Scale Reversed-Phase Columns for the Sensitive Analysis of Complex Peptide Mixtures by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry. J. Mass Spectrom. 1999, 34, 105–116.
Kaufmann, R.; Spengler, B.; Luetzenkirchen, F. Mass Spectrometric Sequencing of Linear Peptides by Product-Ion Analysis in a Reflectron Time-of-Flight Mass Spectrometer Using Matrix-Assisted Laser Desorption Ionization. Rapid Commun. Mass Spectrom. 1993, 7, 902–910.
Shevchenko, A.; Loboda, A.; Ens, W.; Standing, K. G. MALDI Quadrupole Time-of-Flight Mass Spectrometry: A Powerful Tool for Proteomic Research. Anal. Chem. 2000, 72, 2132–2141.
Medzihradszky, K. F.; Campbell, J. M.; Baldwin, M. A.; Falick, A. M.; Juhasz, P.; Vestal, M. L.; Burlingame, A. L. The Characteristics of Peptide Collision-Induced Dissociation Using a High-Performance MALDI-TOF/TOF Tandem Mass Spectrometer. Anal. Chem. 2000, 72, 552–558.
Wilm, M.; Mann, M. Analytical Properties of the Nanoelectrospray Ion Source. Anal. Chem. 1996, 68, 1–8.
Wahl, J. H.; Gale, D. C.; Smith, R. D. Sheathless Capillary Electrophoresis-Electrospray Ionization Mass Spectrometry Using 10 m i.d. Capillaries: Analyses of Tryptic Digests of Cytochrome c. J. Chromatogr. A 1994, 659, 217–222.
Davis, M.; Lee, T. Rapid Protein Identification Using a Microscale Electrospray LC/MS System on an Ion Trap Mass Spectrometer. J. Am. Soc. Mass Spectrom. 1998, 9, 194–201.
Martin, S. E.; Shabanowitz, J.; Hunt, D. F.; Marto, J. A. Subfemtomole MS and MS/MS Peptide Sequence Analysis Using Nano-HPLC Micro-ESI Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. Anal. Chem. 2000, 72, 4266–4274.
Gatlin, C.; Kleemann, G.; Hays, L.; Link, A.; Yates, J. Protein Identification at the Low Femtomole Level from Silver-Stained Gels Using a New Fritless Electrospray Interface for Liquid Chromatrography-Microspray and Nanospray Mass Spectrometry. Anal. Biochem. 1998, 263, 93–101.
Stafford, G. C.; Kelley, P. E.; Syka, J. E. P.; Reynolds, W. E.; Todd, J. F. J. Recent Improvements in Analytical Applications of Ion Trap Technology. Int. J. Mass Spectrom. Ion Processes 1984, 60, 85–98.
Morris, H. R.; Paxton, T.; Dell, A.; Langhorne, J.; Berg, M.; Bordoli, R. S.; Hoyes, J.; Bateman, R. H. High Sensitivity Collisionally-Activated Decomposition Tandem Mass Spectrometry on a Novel Quadrupole/Orthogonal-Acceleration Time-of-flight Mass Spectrometer. Rapid Commun. Mass Spectrom. 1996, 10, 889–896.
Benson, D. A.; Karsch-Mizrachi, I.; Lipman, D. J.; Ostell, J. A.; Rapp, B. A.; Wheeler, D. L. GenBank. Nucleic Acids Res. 2002, 30, 17–20.
Ideker, T.; Thorsson, V.; Ranish, J. A.; Christmas, R.; Buhler, J.; Eng, J. K.; Bumgarner, R.; Goodlett, D. R.; Aebersold, R.; Hood, L. Integrated Genomic and Proteomic Analyses of a Systematically Perturbed Metabolic Network. Science 2001, 292, 929–934.
Celis, J. E.; Palsdottir, H.; Ostergaard, M.; Gromov, P.; Primdahl, H.; Orntoft, T. F.; Wolf, H.; Celis, A.; Gromova, I. Proteomic Strategies to Reveal Tumor Heterogeneity among Urothelial Papillomas. Mol. Cell Proteomics 2002, 1, 269–279.
Steen, H. K. B.; Fernandez, M.; Pandey, A.; Mann, M. Tyrosine Phosphorylation Mapping of the Epidermal Growth Factor Receptor Signaling Pathway. J. Biol. Chem. 2002, 277, 1031–1039.
Chen, L. S.; Shou, W.; Deshaies, R. J.; Annan, R. S.; Carr, S. A. Mass Spectrometry-Based Methods for Phosphorylation Site Mapping of Hyperphosphorylated Proteins Applied to Net1, a Regulator of Exit from Mitosis in Yeast. Mol. Cell Proteomics 2002, 1, 204–212.
Rout, M. P.; Aitchison, J. D.; Suprapto, A.; Hjertaas, K.; Zhao, Y.; Chait, B. T. The Yeast Nuclear Pore Complex: Composition, Architecture, and Transport Mechanism. J. Cell Biol. 2000, 148, 635–652.
Allen, N. P.; Patel, S. S.; Huang, L.; Chalkley, R. J.; Burlingame, A.; Lutzmann, M.; Hurt, E. C.; Rexach, M. Deciphering Networks of Protein Interactions at the Nuclear Pore Complex. Mol. Cell Proteomics 2002, 1, 930–946.
Deshaies, R. J.; Seol, J. H.; McDonald, W. H.; Cope, G.; Lyapina, S.; Shevchenko, A.; Verma, R.; Yates, J. R., III. Charting the Protein Complexome in Yeast by Mass Spectrometry. Mol. Cell Proteomics 2002, 1, 3–10.
Ho, Y.; Gruhler, A.; Heilbut, A.; Bader, G. D.; Moore, L.; Adams, S. L.; Millar, A.; Taylor, P.; Bennett, K.; Boutilier, K.; Yang, L. Y.; Wolting, C.; Donaldson, I.; Schandorff, S.; Shewnarane, J.; Vo, M.; Taggart, J.; Goudreault, M.; Muskat, B.; Alfarano, C.; Dewar, D.; Lin, Z.; Michalickova, K.; Willems, A. R.; Sassi, H.; Figeys, D.; Tyers, M. Systematic Identification of Protein Complexes in Saccharomyces cerevisiae by Mass Spectrometry. Nature 2002, 415, 180–183.
Gavin, A. C.; Bosche, M.; Krause, R.; Grandi, P.; Marzioch, M.; Bauer, A.; Schultz, J.; Rick, J. M.; Michon, A. M.; Cruciat, C. M.; Remor, M.; Hofert, C.; Schelder, M.; Brajenovic, M.; Ruffner, H.; Merino, A.; Klein, K.; Hudak, M.; Dickson, D.; Rudi, T.; Gnau, V.; Bauch, A.; Bastuck, S.; Huhse, B.; Leutwein, C.; Heurtier, M. A.; Copley, R. R.; Edelmann, A.; Querfurth, E.; Rybin, V.; Drewes, G.; Raida, M.; Bouwmeester, T.; Bork, P.; Seraphin, B.; Kuster, B. Functional Organization of the Yeast Proteome by Systematic Analysis of Protein Complexes. Nature 2002, 415, 141–147.
Garin, J. D. R.; Kieffer, S.; Dermine, J. F.; Duclos, S.; Gagnon, E.; Sadoul, R.; Rondeau, C.; Desjardins, M. The Phagosome Proteome: Insight into Phagosome Functions. J. Cell Biol. 2001, 152, 165–180.
Andersen, J. S.; Lyon, C. E.; Fox, A. H.; Leung, A. K.; Lam, Y. W.; Steen, H.; Mann, M.; Lamond, A. I. Directed Proteomic Analysis of the Human Nucleolus. Curr. Biol. 2002, 12, 1–11.
Huber, L. A. Is Proteomics Heading in the Wrong Direction?. Nature Rev. Mol. Cell Biol. 2003, 74–80.
MacCoss, M. J.; McDonald, W. H.; Saraf, A.; Sadygov, R.; Clark, J. M.; Tasto, J. J.; Gould, K. L.; Wolters, D.; Washburn, M.; Weiss, A.; Clark, J. I.; Yates, J. R. Shotgun Identification of Protein Modifications from Protein Complexes and Lens Tissue. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 7900–7905.
Lubman, D. A.; Kachman, M. T.; Wang, H. X.; Gong, S. Y.; Yan, F.; Hamler, R. L.; O’Neil, K. A.; Zhu, K.; Buchanan, N. S.; Barder, T. J. Two-Dimensional Liquid Separations-Mass Mapping of Proteins from Human Cancer Cell Lysates. J. Chromatogr. B 2002, 782, 183–196.
Perkins, D. N.; Pappin, D. J. C.; Creasy, D. M.; Cottrell, S. Probability-Based Protein Identification by Searching Sequence Databases Using Mass Spectrometry Data. Electrophoresis 1999, 20, 3551–3567.
Zhang, W. Z.; Chait, B. T. Profound: An Expert System for Protein Identification Using Mass Spectrometric Peptide Mapping Information. Anal. Chem. 2000, 72, 2482–2489.
Eriksson, J.; Fenyö, D. A Model of Random Mass-Matching and Its Use for Automated Significance Testing in Mass Spectrometric Proteome Analysis. Proteomics 2002, 2, 1615–9861.
Fenyö, D.; Beavis, R. C. A Method for Assessing the Statistical Significance of Mass Spectrometry-Based Protein Identifications Using General Scoring Schemes. Anal. Chem. 2003, 75, 768–774.
Taylor, C. F.; Paton, N. W.; Garwood, K. L.; Kirb, P. D.; Stead, D. A.; Yin, Z.; Deutsch, E. W.; Selway, L.; Walker, J.; Riba-Garcia, I.; Mohammed, S.; Deery, M. J.; Howard, J. A.; Dunkley, T.; Aebersold, R.; Kell, D. B.; Lilley, K. S.; Roepstorff, P.; Yates, J. R., III; Brass, A.; Brown, A. J. P.; Cash, P.; Gaskell, S. J.; Hubbard, S. J.; Oliver, S. G. A Systematic Approach to Modeling, Capturing, and Disseminating Proteomics Experimental Data. Nat. Biotech. 2003, 21, 247–254.
Author information
Authors and Affiliations
Corresponding author
Additional information
Published online July 24, 2003
Rights and permissions
About this article
Cite this article
Henzel, W.J., Watanabe, C. & Stults, J.T. Protein identification: The origins of peptide mass fingerprinting. J Am Soc Mass Spectrom 14, 931–942 (2003). https://doi.org/10.1016/S1044-0305(03)00214-9
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1016/S1044-0305(03)00214-9