Skip to main content
SpringerLink
Log in

Application of Mass Spectrometry to Study Proteomics and Interactomics in Cystic Fibrosis

  • Protocol
  • First Online:
Cystic Fibrosis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 742))

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) does not function in isolation, but rather in a complex network of protein–protein interactions that dictate the physiology of a healthy cell and tissue and, when defective, the pathophysiology characteristic of cystic fibrosis (CF) disease. To begin to address the organization and operation of the extensive cystic fibrosis protein network dictated by simultaneous and sequential interactions, it will be necessary to understand the global protein environment (the proteome) in which CFTR functions in the cell and the local network that dictates CFTR folding, trafficking, and function at the cell surface. Emerging mass spectrometry (MS) technologies and methodologies offer an unprecedented opportunity to fully characterize both the proteome and the protein interactions directing normal CFTR function and to define what goes wrong in disease. Below we provide the CF investigator with a general introduction to the capabilities of modern mass spectrometry technologies and methodologies with the goal of inspiring further application of these technologies for development of a basic understanding of the disease and for the identification of novel pathways that may be amenable to therapeutic intervention in the clinic.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Riordan, J. R. (2008) CFTR function and prospects for therapy. Annu Rev Biochem 77, 701–726.

    PubMed  CAS  Google Scholar 

  2. Wang, X., Venable, J., LaPointe, P., Hutt, D. M., Koulov, A. V., Coppinger, J., et al. (2006) Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis. Cell 127, 803–815.

    PubMed  CAS  Google Scholar 

  3. Kumar, C., and Mann, M. (2009) Bioinformatics analysis of mass spectrometry-based proteomics data sets. FEBS Lett 583, 1703–1712.

    PubMed  CAS  Google Scholar 

  4. Yates, J. R., Ruse, C. I., and Nakorchevsky, A. (2009) Proteomics by mass spectrometry: approaches, advances, and applications. Annu Rev Biomed Eng 11, 49–79.

    PubMed  CAS  Google Scholar 

  5. Davezac, N., Tondelier, D., Lipecka, J., Fanen, P., Demaugre, F., Debski, J., et al. (2004) Global proteomic approach unmasks involvement of keratins 8 and 18 in the delivery of cystic fibrosis transmembrane conductance regulator (CFTR)/deltaF508-CFTR to the plasma membrane. Proteomics 4, 3833–3844.

    PubMed  CAS  Google Scholar 

  6. Roxo-Rosa, M., Davezac, N., Bensalem, N., Majumder, M., Heda, G. D., Simas, A., et al. (2004) Proteomics techniques for cystic fibrosis research. J Cyst Fibros 3, 85–89.

    PubMed  CAS  Google Scholar 

  7. Singh, O. V., Pollard, H. B., and Zeitlin, P. L. (2008) Chemical rescue of deltaF508-CFTR mimics genetic repair in cystic fibrosis bronchial epithelial cells. Mol Cell Proteomics 7, 1099–1110.

    PubMed  CAS  Google Scholar 

  8. Pollard, H. B., Eidelman, O., Jozwik, C., Huang, W., Srivastava, M., Ji, X. D., et al. (2006) De novo biosynthetic profiling of high abundance proteins in cystic fibrosis lung epithelial cells. Mol Cell Proteomics 5, 1628–1637.

    PubMed  CAS  Google Scholar 

  9. Singh, O. V., Vij, N., Mogayzel, P. J., Jr., Jozwik, C., Pollard, H. B., and Zeitlin, P. L. (2006) Pharmacoproteomics of 4-phenylbutyrate-treated IB3-1 cystic fibrosis bronchial epithelial cells. J Proteome Res 5, 562–571.

    PubMed  CAS  Google Scholar 

  10. Pollard, H. B., Ji, X. D., Jozwik, C., and Jacobowitz, D. M. (2005) High abundance protein profiling of cystic fibrosis lung epithelial cells. Proteomics 5, 2210–2226.

    PubMed  CAS  Google Scholar 

  11. Penque, D. (2007) Proteomic biomarker discovery for the monogenic disease cystic fibrosis. Expert Rev Proteomics 4, 199–209.

    PubMed  CAS  Google Scholar 

  12. Gomes-Alves, P., Imrie, M., Gray, R. D., Nogueira, P., Ciordia, S., Pacheco, P., et al. (2010) SELDI-TOF biomarker signatures for cystic fibrosis, asthma and chronic obstructive pulmonary disease. Clin Biochem 43, 168–177.

    PubMed  CAS  Google Scholar 

  13. Gharib, S. A., Vaisar, T., Aitken, M. L., Park, D. R., Heinecke, J. W., and Fu, X. (2009) Mapping the lung proteome in cystic fibrosis. J Proteome Res 8, 3020–3028.

    PubMed  CAS  Google Scholar 

  14. Chang, D. W., Hayashi, S., Gharib, S. A., Vaisar, T., King, S. T., and Tsuchiya, M. (2008) Proteomic and computational analysis of bronchoalveolar proteins during the course of the acute respiratory distress syndrome. Am J Respir Crit Care Med 178, 701–709.

    PubMed  CAS  Google Scholar 

  15. Fu, X., Gharib, S. A., Green, P. S., Aitken, M. L., Frazer, D. A., Park, D. R., et al. (2008) Spectral index for assessment of differential protein expression in shotgun proteomics. J Proteome Res 7, 845–854.

    PubMed  CAS  Google Scholar 

  16. Gray, R. D., MacGregor, G., Noble, D., Imrie, M., Dewar, M., Boyd, A. C., et al. (2008) Sputum proteomics in inflammatory and suppurative respiratory diseases. Am J Respir Crit Care Med 178, 444–452.

    PubMed  CAS  Google Scholar 

  17. MacGregor, G., Gray, R. D., Hilliard, T. N., Imrie, M., Boyd, A. C., Alton, E. W., et al. (2008) Biomarkers for cystic fibrosis lung disease: application of SELDI-TOF mass spectrometry to BAL fluid. J Cyst Fibros 7, 352–358.

    PubMed  CAS  Google Scholar 

  18. Nicholas, B. L., O’Connor, C. D., and Djukanovic, R. (2009) From proteomics to prescription-the search for COPD biomarkers. COPD 6, 298–303.

    PubMed  Google Scholar 

  19. Nicholas, B., and Djukanovic, R. (2009) Induced sputum: a window to lung pathology. Biochem Soc Trans 37, 868–872.

    PubMed  CAS  Google Scholar 

  20. Nicholas, B., Skipp, P., Mould, R., Rennard, S., Davies, D. E., O‘Connor, C. D., et al. (2006) Shotgun proteomic analysis of human-induced sputum. Proteomics 6, 4390–4401.

    PubMed  CAS  Google Scholar 

  21. Lau, A. T., and Chiu, J. F. (2009) Biomarkers of lung-related diseases: current knowledge by proteomic approaches. J Cell Physiol 221, 535–543.

    PubMed  CAS  Google Scholar 

  22. Thelin, W. R., Chen, Y., Gentzsch, M., Kreda, S. M., Sallee, J. L., Scarlett, C. O., et al. (2007) Direct interaction with filamins modulates the stability and plasma membrane expression of CFTR. J Clin Invest 117, 364–374.

    PubMed  CAS  Google Scholar 

  23. Gomes-Alves, P., Neves, S., Coelho, A. V., and Penque, D. (2009) Low temperature restoring effect on F508del-CFTR misprocessing: a proteomic approach. J Proteomics 73, 218–230.

    PubMed  CAS  Google Scholar 

  24. Gomes-Alves, P., Couto, F., Pesquita, C., Coelho, A. V., and Penque, D. (2010) Rescue of F508del-CFTR by RXR motif inactivation triggers proteome modulation associated with the unfolded protein response. Biochim Biophys Acta 1804, 856–865.

    PubMed  CAS  Google Scholar 

  25. Jiang, H., Ramos, A. A., and Yao, X. (2010) Targeted quantitation of overexpressed and endogenous cystic fibrosis transmembrane conductance regulator using multiple reaction monitoring tandem mass spectrometry and oxygen stable isotope dilution. Anal Chem 82, 336–342.

    PubMed  CAS  Google Scholar 

  26. Yates, J., Ruse, C. I., and Nakorchevsky, A. (2009) Proteomics by mass spectrometry: approaches, advances, and applications. Annu Rev Biomed Eng 11, 49–79.

    PubMed  CAS  Google Scholar 

  27. Hillenkamp, F., and Karas, M. (1990) Mass spectrometry of peptides and proteins by matrix-assisted ultraviolet laser desorption/ionization. Methods Enzymol 193, 280–295.

    PubMed  CAS  Google Scholar 

  28. Tanaka, K. (2003) The origin of macromolecule ionization by laser irradiation (Nobel Lecture). Angew Chem Int Ed Engl 42, 3860–3870.

    PubMed  Google Scholar 

  29. Fenn, J. B., Mann, M., Meng, C. K., Wong, S. F., and Whitehouse, C. M. (1989) Electrospray ionization for mass spectrometry of large biomolecules. Science 246, 64–71.

    PubMed  CAS  Google Scholar 

  30. Silvertand, L. H., Torano, J. S., de Jong, G. J., and van Bennekom, W. P. (2008) Improved repeatability and matrix-assisted desorption/ionization – time of flight mass spectrometry compatibility in capillary isoelectric focusing. Electrophoresis 29, 1985–1996.

    PubMed  CAS  Google Scholar 

  31. Zheng, J., Li, N., Ridyard, M., Dai, H., Robbins, S. M., and Li, L. (2005) Simple and robust two-layer matrix/sample preparation method for MALDI MS/MS analysis of peptides. J Proteome Res 4, 1709–1716.

    PubMed  CAS  Google Scholar 

  32. Chen, Y., Wall, D., and Lubman, D. M. (1998) Rapid identification and screening of proteins from whole cell lysates of human erythroleukemia cells in the liquid phase, using non-porous reversed phase high-performance liquid chromatography separations of proteins followed by matrix-assisted laser desorption/ionization mass spectrometry analysis and sequence database searching. Rapid Commun Mass Spectrom 12, 1994–2003.

    PubMed  CAS  Google Scholar 

  33. Shen, Y., Zhao, R., Belov, M. E., Conrads, T. P., Anderson, G. A., Tangm, K., et al. (2001) Packed capillary reversed-phase liquid chromatography with high-performance electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry for proteomics. Anal Chem 73, 1766–1775.

    PubMed  CAS  Google Scholar 

  34. Laiko, V. V., Baldwin, M. A., and Burlingame, A. L. (2000) Atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry. Anal Chem 72, 652–657.

    PubMed  CAS  Google Scholar 

  35. Merchant, M., and Weinberger, S. R. (2000) Recent advancements in surface-enhanced laser desorption/ionization-time of flight-mass spectrometry. Electrophoresis 21, 1164–1177.

    PubMed  CAS  Google Scholar 

  36. Felitsyn, N., Peschke, M., and Kebarle, P. (2002) Origin and number of charges observed on multiply-protonated native proteins produced by ESI. Int J Mass Spectrom 219, 39–62.

    CAS  Google Scholar 

  37. Shen, Y., Moore, R. J., Zhao, R., Blonder, J., Auberry, D. L., Masselon, C., et al. (2003) High-efficiency on-line solid-phase extraction coupling to 15-150-microm-i.d. column liquid chromatography for proteomic analysis. Anal Chem 75, 3264–3273.

    Google Scholar 

  38. Shen, Y., and Smith, R. D. (2002) Proteomics based on high-efficiency capillary separations. Electrophoresis 23, 3106–3124.

    PubMed  CAS  Google Scholar 

  39. Edmond de Hoffmann, V. S. (2007) Mass Spectrometry, 3rd ed. Wiley, London, p. 489.

    Google Scholar 

  40. Han, X., Aslanian, A., and Yates, J. R., 3rd. (2008) Mass spectrometry for proteomics. Curr Opin Chem Biol 12, 483–490.

    PubMed  CAS  Google Scholar 

  41. Yates, J. R., 3rd. (2004) Mass spectral analysis in proteomics. Annu Rev Biophys Biomol Struct 33, 297–316.

    PubMed  CAS  Google Scholar 

  42. Liu, T., Belov, M. E., Jaitly, N., Qian, W. J., and Smith, R. D. (2007) Accurate mass measurements in proteomics. Chem Rev 107, 3621–3653.

    PubMed  CAS  Google Scholar 

  43. Perry, R. H., Cooks, R. G., and Noll, R. J. (2008) Orbitrap mass spectrometry: instrumentation, ion motion and applications. Mass Spectrom Rev 27, 661–699.

    PubMed  CAS  Google Scholar 

  44. Brancia, F. L. (2006) Recent developments in ion-trap mass spectrometry and related technologies. Expert Rev Proteomics 3, 143–151.

    PubMed  CAS  Google Scholar 

  45. Domon, B., and Aebersold, R. (2006) Mass spectrometry and protein analysis. Science 312, 212–217.

    PubMed  CAS  Google Scholar 

  46. Hager, J. W. (2003) Product ion spectral simplification using time-delayed fragment ion capture with tandem linear ion traps. Rapid Commun Mass Spectrom 17, 1389–1398.

    PubMed  CAS  Google Scholar 

  47. Hardman, M., and Makarov, A. A. (2003) Interfacing the orbitrap mass analyzer to an electrospray ion source. Anal Chem 75, 1699–1705.

    PubMed  CAS  Google Scholar 

  48. Hu, Q., Noll, R. J., Li, H., Makarov, A., Hardman, M., and Graham Cooks, R. (2005) The orbitrap: a new mass spectrometer. J Mass Spectrom 40, 430–443.

    PubMed  CAS  Google Scholar 

  49. Makarov, A., Denisov, E., Lange, O., and Horning, S. (2006) Dynamic range of mass accuracy in LTQ orbitrap hybrid mass spectrometer. J Am Soc Mass Spectrom 17, 977–982.

    PubMed  CAS  Google Scholar 

  50. Syka, J. E., Coon, J. J., Schroeder, M. J., Shabanowitz, J., and Hunt, D. F. (2004) Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry. Proc Natl Acad Sci USA 101, 9528–9533.

    PubMed  CAS  Google Scholar 

  51. Breuker, K., Jin, M., Han, X., Jiang, H., and McLafferty, F. W. (2008) Top-down identification and characterization of biomolecules by mass spectrometry. J Am Soc Mass Spectrom 19, 1045–1053.

    PubMed  CAS  Google Scholar 

  52. Shevchenko, A., Chernushevich, I., Ens, W., Standing, K. G., Thomson, B., Wilm, M., et al. (1997) Rapid “de novo” peptide sequencing by a combination of nanoelectrospray, isotopic labeling and a quadrupole/time-of-flight mass spectrometer. Rapid Commun Mass Spectrom 11, 1015–1024.

    PubMed  CAS  Google Scholar 

  53. Collings, B. A., Campbell, J. M., Mao, D., and Douglas, D. J. (2001) A combined linear ion trap time-of-flight system with improved performance and MS(n) capabilities. Rapid Commun Mass Spectrom 15, 1777–1795.

    PubMed  CAS  Google Scholar 

  54. Douglas, D. J., Frank, A. J., and Mao, D. (2005) Linear ion traps in mass spectrometry. Mass Spectrom Rev 24, 1–29.

    PubMed  CAS  Google Scholar 

  55. Schwartz, J. C., Senko, M. W., and Syka, J. E. (2002) A two-dimensional quadrupole ion trap mass spectrometer. J Am Soc Mass Spectrom 13, 659–669.

    PubMed  CAS  Google Scholar 

  56. Yates, J. R., Cociorva, D., Liao, L., and Zabrouskov, V. (2006) Performance of a linear ion trap-Orbitrap hybrid for peptide analysis. Anal Chem 78, 493–500.

    PubMed  CAS  Google Scholar 

  57. Macek, B., Waanders, L. F., Olsen, J. V., and Mann, M. (2006) Top-down protein sequencing and MS3 on a hybrid linear quadrupole ion trap-orbitrap mass spectrometer. Mol Cell Proteomics 5, 949–958.

    PubMed  CAS  Google Scholar 

  58. Frank, A. M., Pesavento, J. J., Mizzen, C. A., Kelleher, N. L., and Pevzner, P. A. (2008) Interpreting top-down mass spectra using spectral alignment. Anal Chem 80, 2499–2505.

    PubMed  CAS  Google Scholar 

  59. Bakalarski, C. E., Elias, J. E., Villén, J., Haas, W., Gerber, S. A., Everley, P. A., et al. (2008) The impact of peptide abundance and dynamic range on stable-isotope-based quantitative proteomic analyses. J Proteome Res 7, 4756–4765.

    PubMed  CAS  Google Scholar 

  60. Schenk, S., Schoenhals, G. J., Souza, G. D., and Mann, M. (2008) A high confidence, manually validated human blood plasma protein reference set. BMC Med Genomics 1, 41–75.

    PubMed  Google Scholar 

  61. Junqueira, M., Spirin, V., Balbuena, T. S., Thomas, H., Adzhubei, I., Sunyaev, S., et al. (2008) Protein identification pipeline for the homology-driven proteomics. J Proteomics 71, 346–356.

    PubMed  CAS  Google Scholar 

  62. DiMaggio, P. A., Jr., Floudas, C. A., Lu, B., and Yates, J. R., 3rd. (2008) A hybrid method for peptide identification using integer linear optimization, local database search, and quadrupole time-of-flight or OrbiTrap tandem mass spectrometry. J Proteome Res 7, 1584–1593.

    PubMed  CAS  Google Scholar 

  63. Lu, B., Motoyama, A., Ruse, C., Venable, J., and Yates, J. R., 3rd. (2008) Improving protein identification sensitivity by combining MS and MS/MS information for shotgun proteomics using LTQ-Orbitrap high mass accuracy data. Anal Chem 80, 2018–2025.

    PubMed  CAS  Google Scholar 

  64. Herbert, B. R., Harry, J. L., Packer, N. H., Gooley, A. A., Pedersen, S. K., and Williams, K. L. (2001) What place for polyacrylamide in proteomics? Trends Biotechnol 19, S3–S9.

    PubMed  CAS  Google Scholar 

  65. Monteoliva, L., and Albar, J. P. (2004) Differential proteomics: an overview of gel and non-gel based approaches. Brief Funct Genomic Proteomic 3, 220–239.

    PubMed  CAS  Google Scholar 

  66. Braun, R. J., Kinkl, N., Beer, M., and Ueffing, M. (2007) Two-dimensional electrophoresis of membrane proteins. Anal Bioanal Chem 389, 1033–1045.

    PubMed  CAS  Google Scholar 

  67. Cooper, J. W., Wang, Y., and Lee, C. S. (2004) Recent advances in capillary separations for proteomics. Electrophoresis 25, 3913–3926.

    PubMed  CAS  Google Scholar 

  68. Fournier, M. L., Gilmore, J., Martin-Brown, S. A., and Washburn, M. P. (2007) Multidimensional separations-based shotgun proteomics. Chem Rev 107, 3654–3686.

    PubMed  CAS  Google Scholar 

  69. Shen, Y., Zhao, R., Berger, S. J., Anderson, G. A., Rodriguez, N., and Smith, R. D. (2002) High-efficiency nanoscale liquid chromatography coupled on-line with mass spectrometry using nanoelectrospray ionization for proteomics. Anal Chem 74, 4235–4249.

    PubMed  CAS  Google Scholar 

  70. Shen, Y., Strittmatter, E. F., Zhang, R., Metz, T. O., Moore, R. J., Li, F., et al. (2005) Making broad proteome protein measurements in 1–5 min using high-speed RPLC separations and high-accuracy mass measurements. Anal Chem 77, 7763–7773.

    PubMed  CAS  Google Scholar 

  71. Shen, Y., and Smith, R. D. (2005) Advanced nanoscale separations and mass spectrometry for sensitive high-throughput proteomics. Expert Rev Proteomics 2, 431–447.

    PubMed  CAS  Google Scholar 

  72. Anspach, J. A., Maloney, T. D., Brice, R. W., and Colon, L. A. (2005) Injection valve for ultrahigh-pressure liquid chromatography. Anal Chem 77, 7489–7494.

    PubMed  CAS  Google Scholar 

  73. Anspach, J. A., Maloney, T. D., and Colon, L. A. (2007) Ultrahigh-pressure liquid chromatography using a 1–mm id column packed with 1.5-microm porous particles. J Sep Sci 30, 1207–1213.

    PubMed  CAS  Google Scholar 

  74. Motoyama, A., Venable, J. D., Ruse, C. I., and Yates, J. R., 3rd. (2006) Automated ultra-high-pressure multidimensional protein identification technology (UHP-MudPIT) for improved peptide identification of proteomic samples. Anal Chem 78, 5109–5118.

    PubMed  CAS  Google Scholar 

  75. Chi, A., Huttenhower, C., Geer, L. Y., Coon, J. J., Syka, J. E., Bai, D. L., et al. (2007) Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry. Proc Natl Acad Sci USA 104, 2193–2198.

    PubMed  CAS  Google Scholar 

  76. Delahunty, C. M., and Yates, J. R., 3rd. (2007) MudPIT: multidimensional protein identification technology. Biotechniques 43, 563–567.

    PubMed  CAS  Google Scholar 

  77. Stoll, D. R., Wang, X., and Carr, P. W. (2008) Comparison of the practical resolving power of one- and two-dimensional high-performance liquid chromatography analysis of metabolomic samples. Anal Chem 80, 268–278.

    PubMed  CAS  Google Scholar 

  78. Guzzetta, A. W., and Chien, A. S. (2005) A double-vented tetraphasic continuous column approach to mudpit analysis on long capillary columns demonstrates superior proteomic coverage. J Proteome Res 4, 2412–2419.

    PubMed  CAS  Google Scholar 

  79. Shen, Y., Tolić, N., Masselon, C., Pasa-Tolić, L., Camp, D. G., 2nd., Lipton, M. S., et al. (2004) Nanoscale proteomics. Anal Bioanal Chem 378, 1037–1045.

    PubMed  CAS  Google Scholar 

  80. Motoyama, A., Xu, T., Ruse, C. I., Wohlschlegel, J. A., and Yates, J. R., 3rd. (2007) Anion and cation mixed-bed ion exchange for enhanced multidimensional separations of peptides and phosphopeptides. Anal Chem 79, 3623–3634.

    PubMed  CAS  Google Scholar 

  81. Dowell, J. A., Frost, D. C., Zhang, J., and Li, L. (2008) Comparison of two-dimensional fractionation techniques for shotgun proteomics. Anal Chem 80, 6715–6723.

    PubMed  CAS  Google Scholar 

  82. Macek, B., Mann, M., and Olsen, J. V. (2009) Global and site-specific quantitative phosphoproteomics: principles and applications. Annu Rev Pharmacol Toxicol 49, 199–221.

    PubMed  CAS  Google Scholar 

  83. Ficarro, S. B., McCleland, M. L., Stukenberg, P. T., Burke, D. J., Ross, M. M., Shabanowitz, J., et al. (2002) Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nat Biotechnol 20, 301–305.

    PubMed  CAS  Google Scholar 

  84. Tsai, C. F., et al. (2008) Immobilized metal affinity chromatography revisited: pH/Acid control toward high selectivity in phosphoproteomics. J Proteome Res 7, 4058–4069.

    PubMed  CAS  Google Scholar 

  85. Linding, R., Jensen, L. J., Ostheimer, G. J., van Vugt, M. A., Jørgensen, C., Miron, I. M., et al. (2007) Systematic discovery of in vivo phosphorylation networks. Cell 129, 1415–1426.

    PubMed  CAS  Google Scholar 

  86. Feng, S., et al. (2007) Immobilized zirconium ion affinity chromatography for specific enrichment of phosphopeptides in phosphoproteome analysis. Mol Cell Proteomics 6, 1656–1665.

    PubMed  CAS  Google Scholar 

  87. Sykora, C., Hoffmann, R., and Hoffmann, P. (2007) Enrichment of multiphosphorylated peptides by immobilized metal affinity chromatography using Ga(III)- and Fe(III)-complexes. Protein Pept Lett 14, 489–496.

    PubMed  CAS  Google Scholar 

  88. Pinkse, M. W., Uitto, P. M., Hilhorst, M. J., Ooms, B., and Heck, A. J. (2004) Selective isolation at the femtomole level of phosphopeptides from proteolytic digests using 2D-NanoLC-ESI-MS/MS and titanium oxide precolumns. Anal Chem 76, 3935–3943.

    PubMed  CAS  Google Scholar 

  89. Li, K. W., and Jimenez, C. R. (2008) Synapse proteomics: current status and quantitative applications. Expert Rev Proteomics 5, 353–360.

    PubMed  CAS  Google Scholar 

  90. Zhou, M., and Veenstra, T. D. (2007) Proteomic analysis of protein complexes. Proteomics 7, 2688–2697.

    PubMed  CAS  Google Scholar 

  91. Cantin, G. T., et al. (2008) Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res 7, 1346–1351.

    PubMed  CAS  Google Scholar 

  92. Han, G., et al. (2008) Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography. Proteomics 8, 1346–1361.

    PubMed  CAS  Google Scholar 

  93. McNulty, D. E., and Annan, R. S. (2008) Hydrophilic interaction chromatography reduces the complexity of the phosphoproteome and improves global phosphopeptide isolation and detection. Mol Cell Proteomics 7, 971–980.

    PubMed  CAS  Google Scholar 

  94. Zaia, J. (2008) Mass spectrometry and the emerging field of glycomics. Chem Biol 15, 881–892.

    PubMed  CAS  Google Scholar 

  95. Tissot, B., et al. (2009) Glycoproteomics: past, present and future. FEBS Lett 583, 1728–1735.

    PubMed  CAS  Google Scholar 

  96. Wei, X., and Li, L. (2009) Comparative glycoproteomics: approaches and applications. Brief Funct Genom Proteomic 8, 104–113.

    CAS  Google Scholar 

  97. Dai, Z., Zhou, J., Qiu, S. J., Liu, Y. K., and Fan, J. (2009) Lectin-based glycoproteomics to explore and analyze hepatocellular carcinoma-related glycoprotein markers. Electrophoresis 30, 2957–2966.

    PubMed  CAS  Google Scholar 

  98. Yue, T., and Haab, B. B. (2009) Microarrays in glycoproteomics research. Clin Lab Med 29, 15–29.

    PubMed  Google Scholar 

  99. Ito, S., Hayama, K., and Hirabayashi, J. (2009) Enrichment strategies for glycopeptides. Methods Mol Biol 534, 195–203.

    PubMed  CAS  Google Scholar 

  100. Atwood, J. A., 3rd., et al. (2006) Glycoproteomics of trypanosoma cruzi trypomastigotes using subcellular fractionation, lectin affinity, and stable isotope labeling. J Proteome Res 5, 3376–3384.

    PubMed  CAS  Google Scholar 

  101. Yue, G., Luo, Q., Zhang, J., Wu, S. L., and Karger, B. L. (2007) Ultratrace LC/MS proteomic analysis using 10-microm-i.d. Porous layer open tubular poly(styrene-divinylbenzene) capillary columns. Anal Chem 79, 938–946.

    PubMed  CAS  Google Scholar 

  102. Durham, M., and Regnier, F. E. (2006) Targeted glycoproteomics: serial lectin affinity chromatography in the selection of O-glycosylation sites on proteins from the human blood proteome. J Chromatogr 1132, 165–173.

    CAS  Google Scholar 

  103. Spange, S., Wagner, T., Heinzel, T., and Kramer, O. H. H. (2009) Acetylation of non-histone proteins modulates cellular signalling at multiple levels. Int J Biochem Cell Biol 4, 185–198.

    Google Scholar 

  104. Norris, K. L., Lee, J. Y., and Yao, T. P. (2009) Acetylation goes global: the emergence of acetylation biology. Sci Signal 2, 76–83.

    Google Scholar 

  105. Smith, K. T., and Workman, J. L. (2009) Introducing the acetylome. Nat Biotechnol 27, 917–919.

    PubMed  CAS  Google Scholar 

  106. Choudhary, C., et al. (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325, 834–840.

    PubMed  CAS  Google Scholar 

  107. Hutt, D. M., et al. (2010) Reduced histone deacetylase 7 activity restores function to misfolded CFTR in cystic fibrosis. Nat Chem Biol 6, 25–33.

    PubMed  CAS  Google Scholar 

  108. Hutt, D. M., Powers, E. T., and Balch, W. E. (2009) The proteostasis boundary in misfolding diseases of membrane traffic. FEBS Lett 583, 2639–2646.

    PubMed  CAS  Google Scholar 

  109. McDonald, W. H., and Yates, J. R., 3rd. (2003) Shotgun proteomics: integrating technologies to answer biological questions. Curr Opin Mol Ther 5, 302–309.

    PubMed  CAS  Google Scholar 

  110. Chait, B. T. (2006) Chemistry. Mass spectrometry: bottom-up or top-down? Science 314, 65–66.

    PubMed  CAS  Google Scholar 

  111. Eng, J., McCormack, A., and Yates, J. (1994) An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. J Am Soc Mass Spectrom 5, 976–989.

    CAS  Google Scholar 

  112. Anderson, D. C., Li, W., Payan, D. G., and Noble, W. S. (2003) A new algorithm for the evaluation of shotgun peptide sequencing in proteomics: support vector machine classification of peptide MS/MS spectra and SEQUEST scores. J Proteome Res 2, 137–146.

    PubMed  CAS  Google Scholar 

  113. Keller, A., Nesvizhskii, A. I., Kolker, E., and Aebersold, R. (2002) Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal Chem 74, 5383–5392.

    PubMed  CAS  Google Scholar 

  114. MacCoss, M. J., et al. (2002) Shotgun identification of protein modifications from protein complexes and lens tissue. Proc Natl Acad Sci USA 99, 7900–7905.

    PubMed  CAS  Google Scholar 

  115. Perkins, D. N., Pappin, D. J., Creasy, D. M., and Cottrell, J. S. (1999) Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 20, 3551–3567.

    PubMed  CAS  Google Scholar 

  116. Sadygov, R., and Yates, J. R., 3rd. (2003) A hypergeometric probability model for protein identification and validation using tandem mass spectral data and protein sequence databases. Anal Chem 75, 3792–3798.

    PubMed  CAS  Google Scholar 

  117. Tabb, D. L., McDonald, H. W., and Yates, J. R., III (2002) DTASelect and contrast: tools for assembling and comparing protein identifications from shotgun proteomics. J Proteome Res 1, 21–36.

    PubMed  CAS  Google Scholar 

  118. Keller, L. C., Romijn, E. P., Zamora, I., Yates, J. R., 3rd., and Marshall, W. F. (2005) Proteomic analysis of isolated chlamydomonas centrioles reveals orthologs of ciliary-disease genes. Curr Biol 15, 1090–1098.

    PubMed  CAS  Google Scholar 

  119. Moore, R. E., Young, M. K., and Lee, T. D. (2000) Method for screening peptide fragment ion mass spectra prior to database searching. J Am Soc Mass Spectrom 11, 422–426.

    PubMed  CAS  Google Scholar 

  120. Frewen, B., and MacCoss, M. J. (2007) Using bibliospec for creating and searching tandem MS peptide libraries. Curr Protoc Bioinformatics 13 13, 17.

    Google Scholar 

  121. Gygi, S. P., et al. (1999) Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol 17, 994–999.

    PubMed  CAS  Google Scholar 

  122. Bettmer, J., et al. (2009) The emerging role of ICP-MS in proteomic analysis. J Proteomics 72, 989–1005.

    PubMed  CAS  Google Scholar 

  123. Schnolzer, M., Jedrzejewski, P., and Lehmann, W. D. (1996) Protease-catalyzed incorporation of 18O into peptide fragments and its application for protein sequencing by electrospray and matrix-assisted laser desorption/ionization mass spectrometry. Electrophoresis 17, 945–953.

    PubMed  CAS  Google Scholar 

  124. Thompson, A., et al. (2003) Tandem mass tags: a novel quantification strategy for comparative analysis of complex protein mixtures by MS/MS. Anal Chem 75, 1895–1904.

    PubMed  CAS  Google Scholar 

  125. Siuti, N., and Kelleher, N. L. (2007) Decoding protein modifications using top-down mass spectrometry. Nat Methods 4, 817–821.

    PubMed  CAS  Google Scholar 

  126. Zabrouskov, V., et al. (2006) Stepwise deamidation of ribonuclease A at five sites determined by top down mass spectrometry. Biochemistry 45, 987–992.

    PubMed  CAS  Google Scholar 

  127. Hawkridge, A. M., et al. (2005) Quantitative mass spectral evidence for the absence of circulating brain natriuretic peptide (BNP-32) in severe human heart failure. Proc Natl Acad Sci USA 102, 17442–17447.

    PubMed  CAS  Google Scholar 

  128. Uttenweiler-Joseph, S., et al. (2008) Toward a full characterization of the human 20 s proteasome subunits and their isoforms by a combination of proteomic approaches. Methods Mol Biol 484, 111–130.

    PubMed  CAS  Google Scholar 

  129. Pesavento, J. J., Mizzen, C. A., and Kelleher, N. L. (2006) Quantitative analysis of modified proteins and their positional isomers by tandem mass spectrometry: human histone H4. Anal Chem 78, 4271–4280.

    PubMed  CAS  Google Scholar 

  130. Du, Y., Parks, B. A., Sohn, S., Kwast, K. E., and Kelleher, N. L. (2006) Top-down approaches for measuring expression ratios of intact yeast proteins using Fourier transform mass spectrometry. Anal Chem 78, 686–694.

    PubMed  CAS  Google Scholar 

  131. Waanders, L. F., Hanke, S., and Mann, M. (2007) Top-down quantitation and characterization of SILAC-labeled proteins. J Am Soc Mass Spectrom 18, 2058–2064.

    PubMed  CAS  Google Scholar 

  132. Sharma, S., et al. (2007) Proteomic profiling of intact proteins using WAX-RPLC 2-D separations and FTICR mass spectrometry. J Proteome Res 6, 602–610.

    PubMed  CAS  Google Scholar 

  133. Bunger, M. K., Cargile, B. J., Ngunjiri, A., Bundy, J. L., and Stephenson, J. L., Jr. (2008) Automated proteomics of E. coli via top-down electron-transfer dissociation mass spectrometry. Anal Chem 80, 1459–1467.

    PubMed  CAS  Google Scholar 

  134. Krijgsveld, J., et al. (2003) Metabolic labeling of C. elegans and D. melanogaster for quantitative proteomics. Nat Biotechnol 21, 927–931.

    PubMed  CAS  Google Scholar 

  135. Wu, C. C., MacCoss, M. J., Howell, K. E., Matthews, D. E., and Yates, J. R., 3rd. (2004) Metabolic labeling of mammalian organisms with stable isotopes for quantitative proteomic analysis. Anal Chem 76, 4951–4959.

    PubMed  CAS  Google Scholar 

  136. Ong, S. E., et al. (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1, 376–386.

    PubMed  CAS  Google Scholar 

  137. Ong, S. E., and Mann, M. (2005) Mass spectrometry-based proteomics turns quantitative. Nat Chem Biol 1, 252–262.

    PubMed  CAS  Google Scholar 

  138. Ibarrola, N., Molina, H., Iwahori, A., and Pandey, A. (2004) A novel proteomic approach for specific identification of tyrosine kinase substrates using [13C]tyrosine. J Biol Chem 279, 15805–15813.

    PubMed  CAS  Google Scholar 

  139. Gruhler, A., Schulze, W. X., Matthiesen, R., Mann, M., and Jensen, O. N. (2005) Stable isotope labeling of arabidopsis thaliana cells and quantitative proteomics by mass spectrometry. Mol Cell Proteomics 4, 1697–1709.

    PubMed  CAS  Google Scholar 

  140. Gruhler, A., et al. (2005) Quantitative phosphoproteomics applied to the yeast pheromone signaling pathway. Mol Cell Proteomics 4, 310–327.

    PubMed  CAS  Google Scholar 

  141. Spellman, D. S., Deinhardt, K., Darie, C. C., Chao, M. V., and Neubert, T. A. (2008) Stable isotopic labeling by amino acids in cultured primary neurons: application to brain-derived neurotrophic factor-dependent phosphotyrosine-associated signaling. Mol Cell Proteomics 7, 1067–1076.

    PubMed  CAS  Google Scholar 

  142. Kruger, M., et al. (2008) SILAC mouse for quantitative proteomics uncovers kindlin-3 as an essential factor for red blood cell function. Cell 134, 353–364.

    PubMed  Google Scholar 

  143. Ong, S. E., Foster, L. J., and Mann, M. (2003) Mass spectrometric-based approaches in quantitative proteomics. Methods 29, 124–130.

    PubMed  CAS  Google Scholar 

  144. Bendall, S. C., et al. (2008) Prevention of amino acid conversion in SILAC experiments with embryonic stem cells. Mol Cell Proteomics 7, 1587–1597.

    PubMed  CAS  Google Scholar 

  145. Van Hoof, D., et al. (2007) An experimental correction for arginine-to-proline conversion artifacts in SILAC-based quantitative proteomics. Nat Methods 4, 677–678.

    PubMed  Google Scholar 

  146. Park, S. K., Venable, J. D., Xu, T., and Yates, J. R., 3rd. (2008) A quantitative analysis software tool for mass spectrometry-based proteomics. Nat Methods 5, 319–322.

    PubMed  CAS  Google Scholar 

  147. Gygi, S. P., et al. (1999) Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol 17, 994–999.

    PubMed  CAS  Google Scholar 

  148. Ross, P. L., et al. (2004) Multiplexed protein quantitation in saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics 3, 1154–1169.

    PubMed  CAS  Google Scholar 

  149. Gerber, S. A., Rush, J., Stemman, O., Kirschner, M. W., and Gygi, S. P. (2003) Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS. Proc Natl Acad Sci USA 100, 6940–6945.

    PubMed  CAS  Google Scholar 

  150. Beynon, R. J., Doherty, M. K., Pratt, J. M., and Gaskell, S. J. (2005) Multiplexed absolute quantification in proteomics using artificial QCAT proteins of concatenated signature peptides. Nat Methods 2, 587–589.

    PubMed  CAS  Google Scholar 

  151. Hanke, S., Besir, H., Oesterhelt, D., and Mann, M. (2008) Absolute SILAC for accurate quantitation of proteins in complex mixtures down to the attomole level. J Proteome Res 7, 1118–1130.

    PubMed  CAS  Google Scholar 

  152. Choe, L., et al. (2007) 8-plex quantitation of changes in cerebrospinal fluid protein expression in subjects undergoing intravenous immunoglobulin treatment for Alzheimer’s disease. Proteomics 7, 3651–3660.

    PubMed  CAS  Google Scholar 

  153. Schwartz, J., Syka, J., and Quarmby, S. (2005) Improving the fundamentals of MSn on 2D linear ion traps: new ion activation and isolation techniques. Am Soc Mass Spectrom 54, 67–76.

    Google Scholar 

  154. Griffin, T. J., et al. (2007) iTRAQ reagent-based quantitative proteomic analysis on a linear ion trap mass spectrometer. J Proteome Res 6, 4200–4209.

    PubMed  CAS  Google Scholar 

  155. Phanstiel, D., Zhang, Y., Marto, J. A., and Coon, J. J. (2008) Peptide and protein quantification using iTRAQ with electron transfer dissociation. J Am Soc Mass Spectrom 19, 1255–1262.

    PubMed  CAS  Google Scholar 

  156. Liu, H., Sadygov, R. G., and Yates, J. R., 3rd. (2004) A model for random sampling and estimation of relative protein abundance in shotgun proteomics. Anal Chem 76, 4193–4201.

    PubMed  CAS  Google Scholar 

  157. Zybailov, B., Coleman, M. K., Florens, L., and Washburn, M. P. (2005) Correlation of relative abundance ratios derived from peptide ion chromatograms and spectrum counting for quantitative proteomic analysis using stable isotope labeling. Anal Chem 77, 6218–6224.

    PubMed  CAS  Google Scholar 

  158. Mueller, L. N., Brusniak, M. Y., Mani, D. R., and Aebersold, R. (2008) An assessment of software solutions for the analysis of mass spectrometry based quantitative proteomics data. J Proteome Res 7, 51–61.

    PubMed  CAS  Google Scholar 

  159. Everley, P. A., et al. (2006) Enhanced analysis of metastatic prostate cancer using stable isotopes and high mass accuracy instrumentation. J Proteome Res 5, 1224–1231.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Cell Biology, Molecular Biology and Chemical Physiology, The Scripps Research Institute, 92037, La Jolla, CA, USA

    William E. Balch

  2. The Institute for Childhood and Neglected Disease, The Scripps Research Institute, 92037, La Jolla, CA, USA

    William E. Balch

  3. Departments of Chemical Physiology, The Scripps Research Institute, 92037, La Jolla, CA, USA

    John R. Yates III

Authors
  1. William E. Balch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John R. Yates III
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to William E. Balch .

Editor information

Editors and Affiliations

  1. Faculty of Sciences, Centre for Biodiversity & Functional, University of Lisboa, Campo Grande, Lisboa, 1749-016, Portugal

    Margarida D. Amaral

  2. , Department of Physiology, University of Regensburg, Universitätsstr. 31, Regensburg, 93053, Germany

    Karl Kunzelmann

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Balch, W.E., Yates, J.R. (2011). Application of Mass Spectrometry to Study Proteomics and Interactomics in Cystic Fibrosis. In: Amaral, M., Kunzelmann, K. (eds) Cystic Fibrosis. Methods in Molecular Biology, vol 742. Humana Press. https://doi.org/10.1007/978-1-61779-120-8_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-120-8_14

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-119-2

  • Online ISBN: 978-1-61779-120-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation