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The role of sulfur and sulfur isotope dilution analysis in quantitative protein analysis

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Abstract

The element sulfur is almost omnipresent in all natural proteomes and plays a key role in protein quantification. Incorporated in the amino acids cysteine and methionine, it has been served as target for many protein-labeling reactions in classic quantitative proteomic approaches based on electrospray or MALDI mass spectrometry. This critical review discusses the potential and limitations of sulfur isotope dilution analysis (IDA) by inductively coupled plasma—mass spectrometry (ICP-MS) for absolute protein quantification. The development of this approach was made possible due to the improved sensitivity and accuracy of sulfur isotope ratio measurement by ICP-MS in recent years. The unique feature of ICP-MS, compound-independent ionization, enables compound (species)-unspecific sulfur IDA. This has the main advantage that only one generic sulfur standard (i.e., one isotopically labeled sulfur spike) is required to quantify each peptide or protein in a sample provided that they are completely separated in chromatography or electrophoresis and that their identities are known. The principles of this approach are illustrated with selected examples from the literature. The discussion includes also related fields of P/S and metal/S ratio measurements for the determination of phosphorylation degrees of proteins and stoichiometries in metalloproteins, respectively. Emerging new areas and future trends such as protein derivatization with metal tags for improved sensitivity of protein detection in ICP-MS are discussed.

The key role of sulfur in protein quantification

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References

  1. Domon B, Aebersold R (2006) Science 312:212–217

    Article  CAS  Google Scholar 

  2. MacCoss MJ, Matthews DE (2005) Anal Chem 77:294A–302A

    Article  CAS  Google Scholar 

  3. Gygi SP, Rist B, Gerber SA, Turecek F, Gelb MH, Aebersold R (1999) Nat Biotechnol 17:994–999

    Article  CAS  Google Scholar 

  4. Ross PL, Huang YN, Marchese JN, Williamson B, Parker K, Hattan S, Khainovski N, Pillai S, Dey S, Daniels S, Purkayastha S, Juhasz P, Martin S, Bartlet-Jones M, He F, Jacobson A, Pappin DJ (2004) Mol Cel Proteom 3:1154–1169

    Article  CAS  Google Scholar 

  5. Wu WW, Wang G, Baek SJ, Shen RF (2006) J Proteome Res 5:651–658

    Article  CAS  Google Scholar 

  6. Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A, Mann M (2002) Mol Cel Proteom 1:376–386

    Article  CAS  Google Scholar 

  7. Gerber SA, Rush J, Stemman O, Kirschner MW, Gygi SP (2003) Proc Natl Acad Sci USA 100:6940–6945

    Article  CAS  Google Scholar 

  8. Mayya V, Han DK (2006) Expert Rev Proteomics 3:597–610

    Article  CAS  Google Scholar 

  9. Heumann KG (1992) Mass Spectrom Rev 11:41–67

    Article  CAS  Google Scholar 

  10. Heumann KG, Gallus SM, Radlinger G, Vogl J (1998) J Anal Atom Spectrom 13:1001–1008

    Google Scholar 

  11. Polatajko A, Ruiz Encinar J, Schaumlöffel D, Szpunar J (2005) Chem Anal [Warsaw] 50:265–278

    CAS  Google Scholar 

  12. Harrington CF, Vidler DS, Watts MJ, Hall JF (2005) Anal Chem 77:4034–4041

    Article  CAS  Google Scholar 

  13. Heumann KG, Rottmann L, Vogl J (1994) J Anal Atom Spectrom 9:1351–1355

    Google Scholar 

  14. Rottmann L, Heumann KG (1994) Fresenius J Anal Chem 350:221–227

    Article  CAS  Google Scholar 

  15. Hinojosa Reyes L, Marchante-Gayon JM, Garcia Alonso JI, Sanz-Medel A (2003) J Anal Atom Spectrom 18:1210–1216

    Google Scholar 

  16. del Castillo Busto ME, Montes-Bayon M, Sanz-Medel A (2006) Anal Chem 78:8218–8226

    Article  Google Scholar 

  17. Schaumlöffel D, Lobinski R (2005) Int J Mass Spectrom 242:217–223

    Article  Google Scholar 

  18. Wind M, Wegener A, Eisenmenger A, Kellner R, Lehmann WD (2003) Angew Chem 42:3425–3427

    Article  CAS  Google Scholar 

  19. Leitner A, Lindner W (2006) Proteomics 6:5418–5434

    Article  CAS  Google Scholar 

  20. Jenkins RE, Kitteringham NR, Hunter CL, Webb S, Hunt TJ, Elsby R, Watson RB, Williams D, Pennington SR, Park BK (2006) Proteomics 6:1934–1947

    Article  CAS  Google Scholar 

  21. Shiio Y, Aebersold R (2006) Nature Protocols 1:139–145

    Article  CAS  Google Scholar 

  22. Schmidt F, Dahlmann B, Janek K, Kloss A, Wacker M, Ackermann R, Thiede B, Jungblut PR (2006) Proteomics 6:4622–4632

    Article  CAS  Google Scholar 

  23. Brittain SM, Ficarro SB, Brock A, Peters EC (2005) Nat Biotechnol 23:463–468

    Article  CAS  Google Scholar 

  24. Conrads TP, Alving K, Veenstra TD, Belov ME, Anderson GA, Anderson DJ, Lipton MS, Pasa-Tolic L, Udseth HR, Chrisler WB, Thrall BD, Smith RD (2001) Anal Chem 73:2132–2139

    Article  CAS  Google Scholar 

  25. Wang S, Regnier FE (2001) J Chromatogr A 924:345–357

    Article  CAS  Google Scholar 

  26. Wang S, Zhang X, Regnier FE (2002) J Chromatogr A 949:153–162

    Article  CAS  Google Scholar 

  27. Liu T, Qian W-J, Strittmatter EF, Camp DG, II, Anderson GA, Thrall BD, Smith RD (2004) Anal Chem 76:5345–5353

    Article  CAS  Google Scholar 

  28. Gevaert K, Van Damme P, Martens L, Vandekerckhove J (2005) Anal Biochem 345:18–29

    Article  CAS  Google Scholar 

  29. Gevaert K, Ghesquière B, Staes A, Martens L, Van Damme J, Thomas GR, Vandekerckhove J (2004) Proteomics 4:897–908

    Article  CAS  Google Scholar 

  30. Staes A, Demol H, Van Damme J, Martens L, Vandekerckhove J, Gevaert K (2004) J Proteome Res 3:786–791

    Article  CAS  Google Scholar 

  31. Shi Y, Xiang R, Crawford JK, Colangelo CM, Horvath C, Wilkins JA (2004) J Proteome Res 3:104–111

    Article  CAS  Google Scholar 

  32. Whetstone PA, Butlin NG, Corneillie TM, Meares CF (2004) Bioconjug Chem 15:3–6

    Article  CAS  Google Scholar 

  33. Seiwert B, Karst U (2007) Anal Bioanal Chem 388:1633–1642

    Google Scholar 

  34. Krause M, Scheler C, Böttger U, Weisshoff H, Linscheid M (2004) German Patent, DE 102 27 599 B4

  35. Takatera K, Watanabe T (1992) Anal Sci 8:469–474

    Article  CAS  Google Scholar 

  36. Wildner H (1998) J Anal Atom Spectrom 13:573–578

    Google Scholar 

  37. Lide DR (1998) (ed) CRC handbook of chemistry and physics, 79th edn. CRC Press, Boca Raton, FL, 10:175

  38. Prohaska T, Latkoczy C, Stingeder G (1999) J Anal Atom Spectrom 14:1501–1504

    Google Scholar 

  39. Riondato J, Vanhaecke F, Moens L, Dams R (1997) J Anal Atom Spectrom 12:933–937

    Google Scholar 

  40. Divjak B, Goessler W (1999) J Chromatogr A 844:161–169

    Article  CAS  Google Scholar 

  41. Menegario AA, Gine MF, Bendassolli JA, Bellato ACS, Trivelin PCO (1998) J Anal Atom Spectrom 13:1065–1067

    Google Scholar 

  42. Bandura DR, Baranov VI, Tanner SD (2002) Anal Chem 74:1497–1502

    Article  CAS  Google Scholar 

  43. Mason PRD, Kaspers K, Van Bergen MJ (1999) J Anal Atom Spectrom 14:1067–1074

    Google Scholar 

  44. Proefrock D, Leonhard P, Prange A (2003) Anal Bioanal Chem 377:132–139

    Article  CAS  Google Scholar 

  45. Schaumlöffel D, Giusti P, Preud’Homme H, Szpunar J, Lobinski R (2007) Anal Chem 79:2859–2868

    Article  Google Scholar 

  46. Schaumlöffel D, Prange A, Marx G, Heumann KG, Bratter P (2002) Anal Bioanal Chem 372:155–163

    Article  Google Scholar 

  47. Polec-Pawlak K, Schaumlöffel D, Szpunar J, Prange A, Lobinski R (2002) J Anal Atom Spectrom 17:908–912

    Google Scholar 

  48. Giusti P, Schaumlöffel D, Ruiz Encinar J, Szpunar J (2005) J Anal Atom Spectrom 20:1101–1107

    Google Scholar 

  49. Giusti P, Lobinski R, Szpunar J, Schaumlöffel D (2006) Anal Chem 78:965–971

    Article  CAS  Google Scholar 

  50. Cohen P (2000) Trends Biochem Sci 25:596–601

    Article  CAS  Google Scholar 

  51. Ptacek J, Snyder M (2006) Trends Genet 22:545–554

    Article  CAS  Google Scholar 

  52. Wind M, Wesch H, Lehmann WD (2001) Anal Chem 73:3006–3010

    Article  CAS  Google Scholar 

  53. Krueger R, Kuebler D, Pallisse R, Burkovski A, Lehmann WD (2006) Anal Chem 78:1987–1994

    Article  CAS  Google Scholar 

  54. Krueger R, Wolschin F, Weckwerth W, Bettmer J, Lehmann WD (2007) Biochem Biophys Res Commun 355:89–96

    Article  CAS  Google Scholar 

  55. Becker JS, Boulyga SF, Becker JS, Pickhardt C, Damoc E, Przybylski M (2003) Int J Mass Spectrom 228:985–997

    Article  CAS  Google Scholar 

  56. Bandura DR, Ornatsky OI, Liao L (2004) J Anal Atom Spectrom 19:96–100

    Google Scholar 

  57. Templeton DM (2005) Selected examples of important metal–protein species. In: Cornelis R, Crews H, Caruso J, Heumann KG (eds) Handbook of elemental speciation, vol II. Wiley, Chichester, UK, pp 638–649

  58. Szpunar J (2005) Analyst 130:442–465

    Article  CAS  Google Scholar 

  59. Hann S, Koellensperger G, Obinger C, Furtmueller PG, Stingeder G (2004) J Anal Atom Spectrom 19:74–79

    Google Scholar 

  60. Hann S, Obinger C, Stingeder G, Paumann M, Furtmueller PG, Koellensperger G (2006) J Anal Atom Spectrom 21:1224–1231

    Google Scholar 

  61. Van Lierde V, Chery CC, Strijckmans K, Galleni M, Devreese B, Van Beeumen J, Moens L, Vanhaecke F (2004) J Anal Atom Spectrom 19:888–893

    Google Scholar 

  62. Rodriguez-Cea A, Fernandez de la Campa MdR, Blanco Gonzalez E, Andon Fernandez B, Sanz-Medel A (2003) J Anal Atom Spectrom 18:1357–1364

  63. Becker JS, Zoriy M, Przybylski M, Becker JS (2007) Int J Mass Spectrom 261:68–73

    Article  CAS  Google Scholar 

  64. Becker JS, Zoriy M, Krause-Buchholz U, Becker JS, Pickhardt C, Przybylski M, Pompe W, Roedel G (2004) J Anal Atom Spectrom 19:1236–1243

    Google Scholar 

Download references

Acknowledgements

This work has been supported by a Marie Curie Intra-European Fellowship for Dr. Christina Rappel of the European Community program FP6-2005-Mobility-5 under contract number MEIF-CT-2006–041246.

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Correspondence to Dirk Schaumlöffel.

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Rappel, C., Schaumlöffel, D. The role of sulfur and sulfur isotope dilution analysis in quantitative protein analysis. Anal Bioanal Chem 390, 605–615 (2008). https://doi.org/10.1007/s00216-007-1607-2

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