Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
권호 표지
DOI QR코드

DOI QR Code

Protein Structural Characterization by Hydrogen/Deuterium Exchange Mass Spectrometry with Top-down Electron Capture Dissociation

  • Received : 2012.12.27
  • Accepted : 2013.02.08
  • Published : 2013.05.20
Download PDF
⟨ Previous Next ⟩

Abstract

This study tested the feasibility of observing H/D exchange of intact protein by top-down electron capture dissociation (ECD) mass spectrometry for the investigation of protein structure. Ubiquitin is selected as a model system. Local structural information was obtained from the deuteration levels of c and $z^{\cdot}$ ions generated from ECD. Our results showed that ${\alpha}$-helix region has the lowest deuteration level and the C-terminal fraction containing a highly mobile tail has the highest deuteration level, which correlates well with previous X-Ray and HDX/NMR analyses. We studied site-specific H/D exchange kinetics by monitoring H/D exchange rate of several structural motives of ubiquitin. Two hydrogen bonded ${\beta}$-strands showed similar HDX rates. However, the outer ${\beta}$-strand always has higher deuteration level than the inner ${\beta}$-strand. The HDX rate of the turn structure (residues 8-11) is lower than that of ${\beta}$-strands (residues 1-7 and residues 12-17) it connects. Although isotopic distribution gets broader after H/D exchange which results in a limited number of backbone cleavage sites detected, our results demonstrate that this method can provide valuable detailed structural information of proteins. This approach should also be suitable for the structural investigation of other unknown proteins, protein conformational changes, as well as protein-protein interactions and dynamics.

Keywords

References

  1. Garcia, R. A.; Pantazatos, D.; Villarreal, F. J. ASSAY and Drug Development Technologies 2004, 2, 81-91. https://doi.org/10.1089/154065804322966342
  2. Wagner, D. S.; Melton, L. G.; Yan, Y. B.; Erickson, B. W.; Anderegg, R. J. Protein Sci. 1994, 3, 1305-1314. https://doi.org/10.1002/pro.5560030817
  3. Kragelund, B. B.; Robinson, C. V.; Knudsen, J.; Dobson, C. M.; Poulsen, F. M. Biochemistry 1995, 34, 7217-7224. https://doi.org/10.1021/bi00021a037
  4. Wales, T. E.; Engen, J. R. Mass Spectrometry Reviews 2006, 25, 158-170. https://doi.org/10.1002/mas.20064
  5. Deng, Y.; Zhang, Z.; Smith, D. L. J. Am. Soc. Mass Spectrom. 1999, 10, 675-684. https://doi.org/10.1016/S1044-0305(99)00038-0
  6. Krishna, M. M. G.; Hoang, L.; Lin, Y.; Englander, S. W. Methods 2004, 34, 51-64. https://doi.org/10.1016/j.ymeth.2004.03.005
  7. Uzawa, T.; Nishimura, C.; Akiyama, S.; Ishimori, K.; Takahashi, S.; Dyson, H. J.; Wright, P. E. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 13859-13864. https://doi.org/10.1073/pnas.0804033105
  8. Kuwata, K.; Shastry, R.; Cheng, H.; Hoshino, M.; Batt, C. A.; Goto, Y.; Roder, H. Nat. Struct. Biol. 2001, 8, 151-155. https://doi.org/10.1038/84145
  9. Roder, H.; Elove, G. A.; Englander, S. W. Nature 1988, 335, 700-704. https://doi.org/10.1038/335700a0
  10. Udgaonkar, J. B.; Baldwin, R. L. Nature 1988, 335, 694-699. https://doi.org/10.1038/335694a0
  11. Engen, J. R.; Smithgall, T. E.; Gmeiner, W. H.; Smith, D. L. Biochemistry 1997, 36, 14384-14391. https://doi.org/10.1021/bi971635m
  12. Bai, Y.; Sosnick, T. R.; Mayne, L.; Englander, S. W. Science 1995, 269, 192-197. https://doi.org/10.1126/science.7618079
  13. Carulla, N.; Barany, G.; Woodward, C. Biophys. Chem. 2002, 101-102, 67-79. https://doi.org/10.1016/S0301-4622(02)00149-7
  14. Parker, M. J.; Marqusee, S. J. Mol. Biol. 2001, 305, 593-602. https://doi.org/10.1006/jmbi.2000.4314
  15. Pan, Y.; Briggs, M. S. Biochemistry 1992, 31, 11405-11412. https://doi.org/10.1021/bi00161a019
  16. Bougault, C.; Feng, L.; Glushka, J.; Kupce, E.; Prestegard, J. H. J. Biomol. NMR 2004, 28, 385-390. https://doi.org/10.1023/B:JNMR.0000015406.66725.30
  17. Dyson, H. J.; Wright, P. E. Chem. Rev. 2004, 104, 3607-3622. https://doi.org/10.1021/cr030403s
  18. Yu, H. Proc. Natl. Acad. Sci. USA. 1999, 96, 332-334. https://doi.org/10.1073/pnas.96.2.332
  19. Katta, V.; Chait, B. T. J. Am. Chem. Soc. 1993, 115, 6317-6321. https://doi.org/10.1021/ja00067a054
  20. Anderegg, R. J.; Wagner, D. S.; Stevenson, C. L.; Borchardt, R. T. J. Am. Soc. Mass Spectrom. 1994, 5, 425-433. https://doi.org/10.1016/1044-0305(94)85058-5
  21. Akashi, S.; Naito, Y.; Takio, K. Anal. Chem. 1999, 71, 4974-4980. https://doi.org/10.1021/ac990444h
  22. Deng, Y.; Pan, H.; Smith, D. L. J. Am. Chem. Soc. 1999, 121, 1966-1967. https://doi.org/10.1021/ja982814+
  23. Kim, M.-Y.; Maier, C. S.; Reed, D. J.; Deinzer, M. L. J. Am. Chem. Soc. 2001, 123, 9860-9866. https://doi.org/10.1021/ja010901n
  24. Demmers, J. A. A.; Rijkers, D. T. S.; Haverkamp, J.; Killian, J. A.; Heck, A. J. R. J. Am. Chem. Soc. 2002, 124, 11191-11198. https://doi.org/10.1021/ja0125927
  25. Cai, X.; Dass, C. Rapid Commun. Mass Spectrom. 2005, 19, 1-8. https://doi.org/10.1002/rcm.1739
  26. Jorgensen, T. J. D.; Gårdsvoll, H.; Ploug, M.; Roepstorff, P. J. Am. Chem. Soc. 2005, 127, 2785-2793. https://doi.org/10.1021/ja043789c
  27. Ferguson, P. L.; Pan, J.; Wilson, D. J.; Dempsey, B.; Lajoie, G.; Shilton, B.; Konermann, L. Anal. Chem. 2007, 79, 153-160. https://doi.org/10.1021/ac061261f
  28. Ferguson, P. L.; Konermann, L. Anal. Chem. 2008, 80, 4078-4086. https://doi.org/10.1021/ac8001963
  29. McLafferty, F. W.; Guan, Z.; Haupts, U.; Wood, T. D.; Kelleher, N. L. J. Am. Chem. Soc. 1998, 120, 4732-4740. https://doi.org/10.1021/ja9728076
  30. Polfer, N. C. Chem. Soc. Rev. 2011, 40, 2211-2221. https://doi.org/10.1039/c0cs00171f
  31. Eyler, J. R. Mass Spectrom. Rev. 2009, 28, 448-467. https://doi.org/10.1002/mas.20217
  32. Hofstadler, S. A.; Sannes-Lowery, K. A.; Griffey, R. H. J. Mass Spectrom. 2000, 35, 62-70. https://doi.org/10.1002/(SICI)1096-9888(200001)35:1<62::AID-JMS913>3.0.CO;2-9
  33. Gauthier, J. W.; Trautman, T. R.; Jacobson, D. B. Anal. Chim. Acta 1991, 246, 211-225. https://doi.org/10.1016/S0003-2670(00)80678-9
  34. Tirado, M.; Rutters, J.; Chen, X.; Yeung, A.; Maarseveen, J.; Eyler, J. R.; Berden, G.; Oomens, J.; Polfer, N. C. J. Am. Soc. Mass Spectrom. 2012, 23, 475-482. https://doi.org/10.1007/s13361-011-0315-5
  35. Barrow, M. P.; Burkitt, W. I.; Derrick, P. J. Analyst 2005, 130, 18-28. https://doi.org/10.1039/b403880k
  36. Zubarev, R. A.; Kelleher, N. L.; McLafferty, F. W. J. Am. Chem. Soc. 1998, 120, 3265-3266. https://doi.org/10.1021/ja973478k
  37. Kleinnijenhuis, A. J.; Duursma, M. C.; Breukink, E.; Heeren, R. M. A.; Heck, A. J. R. Anal. Chem. 2003, 75, 3219-3225. https://doi.org/10.1021/ac0263770
  38. Breuker, K.; Oh, H.; Lin, C.; Carpenter, B. K.; McLafferty, F. W. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 14011-14016. https://doi.org/10.1073/pnas.0406095101
  39. Rand, K. D.; Adams, C. M.; Zubarev, R. A.; Jorgensen, T. J. D. J. Am. Chem. Soc. 2008, 130, 1341-1349. https://doi.org/10.1021/ja076448i
  40. Ge, Y.; Lawhorn, B. G.; EINaggar, M.; Strauss, E.; Park, J.-H.; Begley, T. P.; McLafferty, F. W. J. Am. Chem. Soc. 2002, 124, 672-678. https://doi.org/10.1021/ja011335z
  41. Hagman, C.; Tsybin, Y. O.; Hakansson, P. Rapid Commun. Mass Spectrom. 2006, 20, 661-665. https://doi.org/10.1002/rcm.2339
  42. Charlebois, J. P.; Patrie, S. M.; Kelleher, N. L. Anal. Chem. 2003, 75, 3263-3266. https://doi.org/10.1021/ac020690k
  43. Pan, J.; Han, J.; Borchers, C. H.; Konermann, L. J. Am. Chem. Soc. 2009, 131, 12801-12808. https://doi.org/10.1021/ja904379w
  44. Pan, J.; Han, J.; Borchers, C. H.; Konermann, L. J. Am. Chem. Soc. 2008, 130, 11574-11575. https://doi.org/10.1021/ja802871c
  45. Zehl, M.; Rand, K. D.; Jensen, O. N.; Jorgensen, T. J. D. J. Am. Chem. Soc. 2008, 130, 17453-17459. https://doi.org/10.1021/ja805573h
  46. Sterling, H. J.; Williams, E. R. Anal. Chem. 2010, 82, 9050-9057. https://doi.org/10.1021/ac101957x
  47. Rand, K. D.; Pringle, S. D.; Morris, M.; Brown, J. M. Anal. Chem. 2012, 84, 1931-1940. https://doi.org/10.1021/ac202918j
  48. Vijay-Kumar, S.; Bugg, C. E.; Cook, W. J. J. Mol. Biol. 1987, 194, 531-544. https://doi.org/10.1016/0022-2836(87)90679-6
  49. Vijay-Kumar, S.; Bugg, C. E.; Wilkinson, K. D.; Cook, W. J. Proc. Natl. Acad. Sci. U. S. A. 1985, 82, 3582-3585. https://doi.org/10.1073/pnas.82.11.3582
  50. Briggs, M. S.; Roder, H. Proc. Natl. Acad. Sci. U. S. A. 1992, 89, 2017-2021. https://doi.org/10.1073/pnas.89.6.2017
  51. Di Stefano, D. L.; Wand, A. J. Biochemistry 1987, 26, 7272-7281. https://doi.org/10.1021/bi00397a012
  52. Chen, P.; Gopalacushina, B. G.; Yang, C.; Chan, S. I.; Evans, P. A. Protein Science 2001, 10, 2063-2074. https://doi.org/10.1110/ps.07101
  53. Mohimen, A.; Dobo, A.; Hoerner, J. K.; Kaltashov, I. A. Anal. Chem. 2003, 75, 4139-4147. https://doi.org/10.1021/ac034095+
  54. Liu, Z.; Cheng, S.; Gallie, D. R.; Julian, R. R. Anal. Chem. 2008, 80, 3846-3852. https://doi.org/10.1021/ac800176u
  55. Image from the RCSB PDB (www.pdb.org) of PDB ID 1UBI: Ramage, R.; Green, J.; Muir, T. W.; Ogunjobi, O. M.; Love, S.; Shaw, K. Biochem. J. 1994, 299, 151-158.

Cited by

  1. Mass Spectrometry Methods for Studying Structure and Dynamics of Biological Macromolecules vol.86, pp.1, 2014, https://doi.org/10.1021/ac4039306
  2. Applications of Hydrogen/Deuterium Exchange MS from 2012 to 2014 vol.87, pp.1, 2015, https://doi.org/10.1021/ac5040242
  3. On-tissue Direct Monitoring of Global Hydrogen/Deuterium Exchange by MALDI Mass Spectrometry: Tissue Deuterium Exchange Mass Spectrometry (TDXMS) vol.15, pp.10, 2016, https://doi.org/10.1074/mcp.O116.059832