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Effect of charge on the conformation of highly basic peptides including the tail regions of histone proteins by ion mobility mass spectrometry

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Abstract

The first systematic and comprehensive study of the charging behaviour and effect of charge on the conformation of specifically constructed arginine-rich peptides and its significance to the N- and C-terminal basic tail regions of histone proteins was conducted using ion mobility mass spectrometry (IM-MS). Among the basic amino acids, arginine has the greatest impact on the charging behaviour and structures of gas phase ions by virtue of its high proton affinity. A close linear correlation was found between either the maximum charge, or most abundant charge state, that the peptides support and their average collision cross section (CCS) values measured by ion mobility mass spectrometry. The calculated collision cross sections for the lowest energy solution state models predicted by the PEP-FOLD algorithm using a modified MOBCAL trajectory method were found to best correlate with the values measured by IM-MS. In the case of the histone peptides, more compact folded structures, supporting less than the maximum number of charges, were observed. These results are consistent with those previously reported for histone dimers where neutralization of the charge at the basic residues of the tail regions did not affect their CCS values.

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References

  1. Dyson HJ, Wright PE. Defining solution conformations of small linear peptides. Ann Rev Biophys Biophys Chem. 1991;20:519–38.

    Article  CAS  Google Scholar 

  2. Baldwin RL, Rose GD. Is protein folding hierarchic? I. Local structure and peptide folding. Trends Biochem Sci. 1999;24:26–33.

    Article  CAS  Google Scholar 

  3. Mayo KH, Fields GB. Peptides as models for understanding protein folding. Adv Mol Cell Biol. 1997;22:567–612.

    Article  Google Scholar 

  4. Becker OM, Levy Y, Ravitz O. Flexibility, conformation spaces, and bioactivity. J Phys Chem B. 2000;104:2123–35.

    Article  CAS  Google Scholar 

  5. Moore G. Designing peptide mimetics. Trends Pharmacol Sci. 1994;15:124–9.

    Article  CAS  Google Scholar 

  6. Blundell T, Wood S. The conformation, flexibility, and dynamics of polypeptide hormones. Annu Rev Biochem. 1982;51:123–54.

    Article  CAS  Google Scholar 

  7. Hruby VJ. Designing molecules: specific peptides for specific receptors. Epilepsia. 1989;30:S42–50.

    Article  Google Scholar 

  8. Dyson HJ, Wright PE. Antigenic peptides. FASEB J. 1995;9:37–42.

    CAS  Google Scholar 

  9. Bowie JH, Separovic F, Tyler MJ. Host-defense peptides of Australian anurans. Part 2. Structure, activity, mechanism of action, and evolutionary significance. Peptides. 2012;37:174–88.

    Article  CAS  Google Scholar 

  10. Serpell LC. Alzheimer’s amyloid fibrils: structure and assembly. Biochimica et Biophysica Acta (BBA) - Molecul Basis Dis. 2000;1502:16–30.

    Article  CAS  Google Scholar 

  11. Zhou P, Huang J, editors. Computational peptidology, methods in molecular biology. New York: Springer; 2015.

    Google Scholar 

  12. Craig LC, Cowburn D, Bleich H. Methods for the study of the conformation of small peptide hormones and antibiotics in solution. Annu Rev Biochem. 1975;44:477–90.

    Article  CAS  Google Scholar 

  13. Akashi S. Investigation of molecular interaction within biological macromolecular complexes by mass spectrometry. Med Res Rev. 2006;26:339–68.

    Article  CAS  Google Scholar 

  14. Downard KM. Mass spectrometry of protein interactions. New York: John Wiley and Sons; 2007.

    Book  Google Scholar 

  15. Grandori R. Origin of the conformation dependence of protein charge-state distributions in electrospray ionization mass spectrometry. J Mass Spectrom. 2003;38:11–5.

    Article  CAS  Google Scholar 

  16. Konijnenberga A, Butterera A, Sobott F. Native ion mobility-mass spectrometry and related methods in structural biology. Biochimica et Biophysica Acta Protein Proteom. 1834;2013:1239–56.

    Google Scholar 

  17. Lanucara F, Holman SW, Gray CJ, Eyers CE. The power of ion mobility-mass spectrometry for structural characterization and the study of conformational dynamics. Nat Chem. 2014;6:281–94.

    Article  CAS  Google Scholar 

  18. Downard KM, Maleknia SD, Akashi S. Impact of limited oxidation on protein ion mobility and structure of importance to footprinting by radical probe mass spectrometry. Rapid Commun Mass Spectrom. 2012;26:226–30.

    Article  CAS  Google Scholar 

  19. Akashi S, Maleknia SD, Saikusa K, Downard KM. Stability of the βB2B3 crystallin heterodimer to increased oxidation by radical probe and ion mobility mass spectrometry. J Struct Biol. 2015;189:20–7.

    Article  CAS  Google Scholar 

  20. Maleknia SD, Downard KM. Advances in radical probe mass spectrometry for protein footprinting in chemical biology applications. Chem Soc Rev. 2014;43:3244–58.

    Article  CAS  Google Scholar 

  21. Jarrold MF. Peptides and proteins in the vapor phase. Annu Rev Phys Chem. 2000;52:179–207.

    Article  Google Scholar 

  22. Hilderbrand AE, Clemmer DE. Determination of sequence-specific intrinsic size parameters from cross sections for 162 tripeptides. J Phys Chem B. 2005;109:11802–9.

    Article  CAS  Google Scholar 

  23. Valentine SJ, Ewing M, Dilger JM, Glover M, Geromanos S, Hughes C, et al. Using ion mobility data to improve peptide identification: cross section databases and intrinsic amino acid size parameters. J Proteome Res. 2011;10:2318–29.

    Article  CAS  Google Scholar 

  24. Harvey SR, Macphee CE, Barran PE. Ion mobility mass spectrometry for peptide analysis. Methods. 2011;54:454–61.

    Article  CAS  Google Scholar 

  25. Baldauf C, Rossi M. Going clean: structure and dynamics of peptides in the gas phase and paths to solvation. J. Phys Condens Matter. 2015;27:493002.

  26. Bleiholder C, Dupuis NF, Wyttenbach T, Bowers MT. Ion mobility-mass spectrometry reveals a conformational conversion from random assembly to β-sheet in amyloid fibril formation. Nat Chem. 2011;3:172–7.

    Article  CAS  Google Scholar 

  27. Silveira JA, Fort KL, Pierson NA, Clemmer DE, Russell DH. From solution to the gas phase: stepwise dehydration and kinetic trapping of substance P reveals the origin of peptide conformations. J Am Chem Soc. 2013;135:19147–53.

    Article  CAS  Google Scholar 

  28. Wyttenbach T, Pierson NA, Clemmer DE, Russell DH. Ion mobility analysis of molecular dynamics. Annu Rev Phys Chem. 2014;65:175–96.

    Article  CAS  Google Scholar 

  29. Downard KM, Biemann K. Charging behavior of highly basic peptides during electrospray ionization. A predilection for protons. Int J Mass Spectrom Ion Proc. 1995;148:191–202.

    Article  CAS  Google Scholar 

  30. Downard KM, Biemann K. The effect of charge state and the localization of charge on the collision-induced dissociation of peptide ions. J Am Soc Mass Spectrom. 1993;5:966–75.

    Article  Google Scholar 

  31. Shimoyama S, Nagadoi A, Tachiwana H, Yamada M, Sato M, Kurumizaka H, et al. Deimination stabilizes histone H2A/H2B dimers as revealed by electrospray ionization mass spectrometry. J Mass Spectrom. 2010;45:900–8.

    Article  CAS  Google Scholar 

  32. Saikusa K, Fuchigami S, Takahashi K, Asano Y, Nagadoi A, Tachiwana H, et al. Gas phase structure of the histone multimers characterized by ion mobility mass spectrometry and molecular dynamics simulation. Anal Chem. 2013;85:4165–71.

    Article  CAS  Google Scholar 

  33. Biswas M, Voltz K, Smith JC, Langowski L. Role of histone tails in structural stability of the nucleosome. PLoS Comput Biol. 2011;7:e1002279.

  34. Saikusa K, Nagadoi A, Hara K, Fuchigami S, Kurumizaka H, Nishimura Y, et al. Mass spectrometric approach for characterizing the disordered tail regions of the histone H2A/H2B dimer. Anal Chem. 2015;87:2220–7.

    Article  CAS  Google Scholar 

  35. Saikusa K, Shimoyama S, Asano Y, Nagadoi A, Sato M, Kurumizaka H, et al. Charge neutralization effect of the tail regions on the histone H2A/H2B dimer structure. Protein Sci. 2015;24:1224–31.

    Article  CAS  Google Scholar 

  36. Pringle SD, Giles K, Wildgoose JL, Williams JP, Slade SE, Thalassinos K, et al. An investigation of the mobility separation of some peptide and protein ions using a new hybrid quadrupole/travelling wave IMS/oa-ToF instrument. Int J Mass Spectrom. 2007;261:1–12.

    Article  CAS  Google Scholar 

  37. Giles K, Williams JP, Campuzano I. Enhancements in travelling wave ion mobility resolution. Rapid Commun Mass Spectrom. 2011;25:1559–66.

    Article  CAS  Google Scholar 

  38. Bush MF, Campuzano I, Robinson CV. Ion mobility mass spectrometry of peptide ions: effects of drift gas and calibration strategies. Anal Chem. 2012;84:7124–30.

    Article  CAS  Google Scholar 

  39. Shen Y, Maupetit J, Derreumaux P, Tufféry P. Improved PEP-FOLD approach for peptide and miniprotein structure prediction. J Chem Theor Comp. 2014;10:4745–58.

    Article  CAS  Google Scholar 

  40. DeLano WL. The PyMOL molecular graphics system. (2002);http://www.pymol.org.

  41. Mesleh MF, Hunter JM, Shvartsburg AA, Schatz GC, Jarrold MF. Structural information from ion mobility measurements: effects of the long range potential. J Phys Chem. 1996;100:16082–6.

    Article  CAS  Google Scholar 

  42. Shvartsburg AA, Jarrold MF. An exact hard spheres scattering model for the mobilities of polyatomic ions. Chem Phys Lett. 1996;261:86–91.

    Article  CAS  Google Scholar 

  43. Gronert S, Simpson DC, Conner KM. A reevaluation of computed proton affinities for the common α-amino acids. J Am Soc Mass Spectrom. 2009;20:2116–23.

    Article  CAS  Google Scholar 

  44. Sudha R, Jarrold MF. Left-handed and ambidextrous helices in the gas phase. J Phys Chem B. 2005;109:11777–80.

    Article  CAS  Google Scholar 

  45. Xiao C, Pérez LM, Russell DH. Effects of charge states, charge sites and side chain interactions on conformational preferences of a series of model peptide ions. Analyst. 2015;140:6933–44.

    Article  CAS  Google Scholar 

  46. Marqusee S, Robbins VH, Baldwin RL. Unusually stable helix formation in short alanine-based peptides. Proc Natl Acad Sci U S A. 1989;86:5286–90.

    Article  CAS  Google Scholar 

  47. Shvartsburg AA, Jarrold MF. MobCal. http://www.indiana.edu/~nano/software/.

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Acknowledgments

The Waters Synapt G2 ion mobility mass spectrometer used in these investigations was purchased with funds provided by a Grant-in-Aid for Scientific Research in Innovative Areas (21113003) (to S. Akashi) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. The authors are grateful to Prof. Hajime Tanuma (Tokyo Metropolitan University) who provided an algorithm that allowed for the calculation of peptide theoretical collision cross sections (CCS) in nitrogen gas. The authors thank Asst. Prof. Kazumi Saikusa (Hiroshima University) who implemented the algorithm and helped with their calculation.

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Authors and Affiliations

  1. Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan

    Satoko Akashi & Kevin M. Downard

  2. Faculty of Medicine, University of New South Wales, Sydney, New South Wales, 2052, Australia

    Kevin M. Downard

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  1. Satoko Akashi
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  2. Kevin M. Downard
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Correspondence to Kevin M. Downard.

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Akashi, S., Downard, K.M. Effect of charge on the conformation of highly basic peptides including the tail regions of histone proteins by ion mobility mass spectrometry. Anal Bioanal Chem 408, 6637–6648 (2016). https://doi.org/10.1007/s00216-016-9777-4

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  • DOI: https://doi.org/10.1007/s00216-016-9777-4

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