1932

Abstract

Ion mobility spectrometry-mass spectrometry (IMS-MS) methods are increasingly used to study noncovalent assemblies of peptides and proteins. This review focuses on the noncovalent self-assembly of amino acids and peptides, systems at the heart of the amyloid process that play a central role in a number of devastating diseases. Three different systems are discussed in detail: the 42-residue peptide amyloid-β42 implicated in the etiology of Alzheimer's disease, several amyloid-forming peptides with 6–11 residues, and the assembly of individual amino acids. We also discuss from a more fundamental perspective the processes that determine how quickly proteins and their assemblies denature when the analyte ion has been stripped of its solvent in an IMS-MS measurement and how to soften the measurement so that biologically meaningful data can be recorded.

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2017-06-12
2024-04-24
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Literature Cited

  1. Bowers MT. 1.  2014. Ion mobility spectrometry: a personal view of its development at UCSB. Int. J. Mass Spectrom. 370:75–95 [Google Scholar]
  2. von Helden G, Hsu M-T, Kemper PR, Bowers MT. 2.  1991. Structures of carbon cluster ions from 3 to 60 atoms: linears to rings to fullerenes. J. Chem. Phys. 95:53835 [Google Scholar]
  3. von Helden G, Hsu MT, Gotts N, Bowers MT. 3.  1993. Carbon cluster cations with up to 84 atoms: structures, formation mechanism, and reactivity. J. Phys. Chem. 97:318182–92 [Google Scholar]
  4. von Helden G, Gotts NG, Bowers MT. 4.  1993. Experimental evidence for the formation of fullerenes by collisional heating of carbon rings in the gas phase. Nature 363:60–63 [Google Scholar]
  5. Hunter J, Fye J, Jarrold MF. 5.  1993. Annealing C60+: synthesis of fullerenes and large carbon rings. Science 260:784–86 [Google Scholar]
  6. Kroto HW, Heath JR, O'Brien SC, Curl RF, Smalley RE. 6.  1985. C60: Buckminsterfullerene. Nature 318:162–64 [Google Scholar]
  7. Krätschmer W, Lamb LD, Fostiropoulis K, Huffman DR. 7.  1993. The infrared and ultraviolet absorption spectra of laboratory-produced carbon dust: evidence for the presence of the C60 molecule. Physics and Chemisry of Fullerenes: A Reprint Collection PW Stephens 23–30 River Edge, NJ: World Sci. [Google Scholar]
  8. von Helden G, Gotts NG, Bowers MT. 8.  1993. Annealing of carbon cluster cations: rings to rings and rings to fullerenes. J. Am. Chem. Soc. 115:104363–64 [Google Scholar]
  9. Gotts NG, von Helden G, Bowers MT. 9.  1995. Carbon cluster anions: structure and growth from C5 to C62. Int. J. Mass Spectrom. Ion Process. 149:217–29 [Google Scholar]
  10. Wyttenbach T, von Helden G, Bowers MT. 10.  1996. Gas-phase conformation of biological molecules: bradykinin. J. Am. Chem. Soc. 118:358355–64 [Google Scholar]
  11. Wyttenbach T, Bowers MT. 11.  1999. Gas phase conformations of biological molecules: the hydrogen/deuterium exchange mechanism. J. Am. Soc. Mass Spectrom. 10:19–14 [Google Scholar]
  12. Wyttenbach T, Kemper PR, Bowers MT. 12.  2001. Design of a new electrospray ion mobility mass spectrometer. Int. J. Mass Spectrom. 212:113–23 [Google Scholar]
  13. Kemper PR, Dupuis NF, Bowers MT. 13.  2009. A new, higher resolution, ion mobility mass spectrometer. Int. J. Mass Spectrom. 287:1–346–57 [Google Scholar]
  14. Bernstein SL, Wyttenbach T, Baumketner A. 14.  2005. Amyloid β-protein: monomer structure and early aggregation states of Aβ42 and its Pro19 alloform. J. Am. Chem. Soc. 127:72075–84 [Google Scholar]
  15. Wyttenbach T, Bowers MT. 15.  2011. Structural stability from solution to the gas phase: native solution structure of ubiquitin survives analysis in a solvent-free ion mobility-mass spectrometry environment. J. Phys. Chem. B. 115:4212266–75 [Google Scholar]
  16. Baumketner A, Bernstein S, Wyttenbach T, Bitan G, Teplow DB. 16.  et al. 2006. Amyloid β-protein monomer structure: a computational and experimental study. Protein Sci 15:3420–28 [Google Scholar]
  17. Dupuis NF, Wu C, Shea J-E, Bowers MT. 17.  2009. Human islet amyloid polypeptide monomers form ordered β-hairpins: a possible direct amyloidogenic precursor. J. Am. Chem. Soc. 131:5118283–92 [Google Scholar]
  18. Meier JJ, Kayed R, Lin C-Y. 18.  2006. Inhibition of human IAPP fibril formation does not prevent β-cell death: evidence for distinct actions of oligomers and fibrils of human IAPP. AJP Endocrinol. Metab. 291:6E1317–24 [Google Scholar]
  19. Kirkitadze MD, Bitan G, Teplow DB. 19.  2002. Paradigm shifts in Alzheimer's disease and other neurodegenerative disorders: the emerging role of oligomeric assemblies. J. Neurosci. Res. 69:5567–77 [Google Scholar]
  20. Hardy J, Selkoe DJ. 20.  2002. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297:353–56 [Google Scholar]
  21. Dill KA. 21.  1990. Dominant forces in protein folding. Biochemistry 29:317133–55 [Google Scholar]
  22. Haran G. 22.  2012. How, when and why proteins collapse: the relation to folding. Curr. Opin. Struct. Biol. 22:114–20 [Google Scholar]
  23. Gruebele M. 23.  2002. Protein folding: the free energy surface. Curr. Opin. Struct. Biol. 12:161–68 [Google Scholar]
  24. Dill KA, MacCallum JL. 24.  2012. The protein-folding problem, 50 years on. Science 338:1042–46 [Google Scholar]
  25. Onuchic JN, Wolynes PG. 25.  2004. Theory of protein folding. Curr. Opin. Struct. Biol. 14:170–75 [Google Scholar]
  26. Lazar GA, Desjarlais JR, Handel TM. 26.  1997. De novo design of the hydrophobic core of ubiquitin. Protein Sci 6:61167–78 [Google Scholar]
  27. Johnson EC, Lazar GA, Desjarlais JR, Handel TM. 27.  1999. Solution structure and dynamics of a designed hydrophobic core variant of ubiquitin. Structure 7:8967–76 [Google Scholar]
  28. Wyttenbach T, Bowers MT. 28.  2009. Hydration of biomolecules. Chem. Phys. Lett. 480:1–31–16 [Google Scholar]
  29. Stefani M. 29.  2004. Protein misfolding and aggregation: new examples in medicine and biology of the dark side of the protein world. Biochim. Biophys. Acta 1739:15–25 [Google Scholar]
  30. Paizs B, Suhai S. 30.  2005. Fragmentation pathways of protonated peptides. Mass Spectrom. Rev. 24:4508–48 [Google Scholar]
  31. Wyttenbach T, Paizs B, Barran P, Breci L, Liu D. 31.  et al. 2003. The effect of the initial water of hydration on the energetics, structures, and H/D exchange mechanism of a family of pentapeptides: an experimental and theoretical study. J. Am. Chem. Soc. 125:4513768–75 [Google Scholar]
  32. Meyer T, Gabelica V, Grubmüller H, Orozco M. 32.  2013. Proteins in the gas phase. Wiley Interdiscip. Rev. Comput. Mol. Sci. 3:4408–25 [Google Scholar]
  33. Badman ER, Hoaglund-Hyzer CS, Clemmer DE. 33.  2001. Monitoring structural changes of proteins in an ion trap over ∼10–200 ms: unfolding transitions in cytochrome c ions. Anal Chem 73:246000–7 [Google Scholar]
  34. Breuker K, McLafferty FW. 34.  2008. Stepwise evolution of protein native structure with electrospray into the gas phase, 10−12 to 102 s. PNAS 105:4718145–52 [Google Scholar]
  35. Warnke S, von Helden G, Pagel K. 35.  2013. Protein structure in the gas phase: the influence of side-chain microsolvation. J. Am. Chem. Soc. 135:41177–80 [Google Scholar]
  36. Seo J, Hoffmann W, Warnke S, Bowers MT, Pagel K, vonHelden G. 36.  2016. Retention of native protein structures in the absence of solvent: a coupled ion mobility and spectroscopic study. Angew. Chem. Int. Ed. 55:4514173–76 [Google Scholar]
  37. Silveira JA, Fort KL, Kim D. 37.  2013. From solution to the gas phase: stepwise dehydration and kinetic trapping of substance P reveals the origin of peptide conformations. J. Am. Chem. Soc. 135:5119147–53 [Google Scholar]
  38. Counterman AE, Clemmer DE. 38.  2001. Magic number clusters of serine in the gas phase. J. Phys. Chem. B 105:348092–96 [Google Scholar]
  39. Koeniger SL, Merenbloom SI, Sevugarajan S, Clemmer DE. 39.  2006. Transfer of structural elements from compact to extended states in unsolvated ubiquitin. J. Am. Chem. Soc. 128:3511713–19 [Google Scholar]
  40. Lee S-W, Freivogel P, Schindler T, Beauchamp JL. 40.  1998. Freeze-dried biomolecules: FT-ICR studies of the specific solvation of functional groups and clathrate formation observed by the slow evaporation of water from hydrated peptides and model compounds in the gas phase. J. Am. Chem. Soc. 120:4511758–65 [Google Scholar]
  41. Laskin J, Futrell JH. 41.  2003. Collisional activation of peptide ions in FT-ICR mass spectrometry. Mass Spectrom. Rev. 22:3158–81 [Google Scholar]
  42. McLuckey SA, Goeringer DE. 42.  1997. Slow heating methods in tandem mass spectrometry. J. Mass Spectrom. 32:5461–74 [Google Scholar]
  43. Tolmachev AV, Vilkov AN, Bogdanov B, Păsa-Tolić L, Masselon CD, Smith RD. 43.  2004. Collisional activation of ions in RF ion traps and ion guides: the effective ion temperature treatment. J. Am. Soc. Mass Spectrom. 15:111616–28 [Google Scholar]
  44. Hoxha A, Collette C, De Pauw E, Leyh B. 44.  2001. Mechanism of collisional heating in electrospray mass spectrometry: ion trajectory calculations. J. Phys. Chem. A 105:317326–33 [Google Scholar]
  45. Fernandez-Lima FA, Kaplan DA, Park MA. 45.  2011. Note: integration of trapped ion mobility spectrometry with mass spectrometry. Rev. Sci. Instrum. 82:12126106 [Google Scholar]
  46. Fernandez-Lima F, Kaplan DA, Suetering J, Park MA. 46.  2011. Gas-phase separation using a trapped ion mobility spectrometer. Int. J. Ion Mobil. Spectrom. 14:2–393–98 [Google Scholar]
  47. Langevin MP. 47.  1905. Une formule fondamentale de théorie cinétique. Ann. Chim. Phys. 8:245–88 [Google Scholar]
  48. Mason EA, McDaniel EW. 48.  1988. Transport Properties of Ions in Gases New York: Wiley
  49. Pringle SD, Giles K, Wildgoose JL, Williams JP, Slade SE. 49.  et al. 2007. 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. 261:11–12 [Google Scholar]
  50. Liu FC, Kirk SR, Bleiholder C. 50.  2016. On the structural denaturation of biological analytes in trapped ion mobility spectrometry–mass spectrometry. Analyst 141:123722–30 [Google Scholar]
  51. Bleiholder C. 51.  2016. Towards measuring ion mobilities in non-stationary gases and non-uniform and dynamic electric fields (I). Transport equation. Int. J. Mass Spectrom. 399–400:1–9 [Google Scholar]
  52. Vijay-Kumar S, Bugg CE, Wilkinson KD, Cook WJ. 52.  1985. Three-dimensional structure of ubiquitin at 2.8 A resolution. PNAS 82:113582–85 [Google Scholar]
  53. Bleiholder C, Johnson NR, Contreras S, Wyttenbach T, Bowers MT. 53.  2015. Molecular structures and ion mobility cross sections: analysis of the effects of He and N2 buffer gas. Anal. Chem. 87:147196–203 [Google Scholar]
  54. Benigni P, Marin R, Molano-Arevalo JC. 54.  2016. Towards the analysis of high molecular weight proteins and protein complexes using TIMS–MS. Int. J. Ion Mobil. Spectrom. 19:95 [Google Scholar]
  55. Laszlo KJ, Munger EB, Bush MF. 55.  2016. Folding of protein ions in the gas phase after cation to anion proton transfer reactions (CAPTR). J. Am. Chem. Soc. 138:309581–88 [Google Scholar]
  56. Dahlgren KN, Manelli AM, Stine WB Jr., Baker LK. 56.  et al. 2002. Oligomeric and fibrillar species of amyloid-beta peptides differentially affect neuronal viability. J. Biol. Chem. 277:3532046–53 [Google Scholar]
  57. Suzuki N, Cheung TT, Cai XD. 57.  1994. An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (β APP717) mutants. Science 27:1336–40 [Google Scholar]
  58. Gravina SA, Ho LB, Eckman C. 58.  1995. Amyloid β-protein (Aβ) in Alzheimer's disease brain: biochemical and immunocytochemical analysis with antibodies specific for forms ending at Aβ40 or Aβ42(43). J. Biol. Chem. 270:7013–16 [Google Scholar]
  59. Bitan G, Kirkitadze MD, Lomakin A, Vollers SS, Benedek GB, Teplow DB. 59.  2003. Amyloid β-protein (Aβ) assembly: Aβ40 and Aβ42 oligomerize through distinct pathways. PNAS 100:1330–35 [Google Scholar]
  60. Bernstein SL, Dupuis NF, Lazo ND, Wyttenbach T, Condron MM. 60.  et al. 2009. Amyloid-β protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease. Nat. Chem. 1:4326–31 [Google Scholar]
  61. Murray MM, Bernstein S, Nyugen V, Condron MM, Teplow D, Bowers MT. 61.  2009. Amyloid β-protein: Aβ40 inhibits Aβ42 oligomerization. J. Am. Chem. Soc. 131:6316–17 [Google Scholar]
  62. Lesné S, Koh MT, Kotilinek L, Glabe CG, Yang A. 62.  et al. 2006. A specific amyloid-β protein assembly in the brain impairs memory. Nature 440:352–57 [Google Scholar]
  63. Cheng IH, Scearce-Levie K, Legleiter J, Palop JJ, Gerstein H. 63.  et al. 2007. Accelerating amyloid-β fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models. J. Biol. Chem. 282:3323818–28 [Google Scholar]
  64. Economou NJ, Giammona MJ, Do TD, Zheng X, Teplow DB. 64.  et al. 2016. Amyloid β-protein assembly and Alzheimer's disease: dodecamers of Aβ42, but not of Aβ40, seed fibril formation. J. Am. Chem. Soc. 138:61772–75 [Google Scholar]
  65. Walsh DM, Lomakin A, Benedek GB, Condron MM, Teplow DB. 65.  1997. Amyloid β-protein fibrillo-genesis detection of a protofibrillar intermediate. J. Biol. Chem. 272:3522364–72 [Google Scholar]
  66. Gessel MM, Bernstein S, Kemper M, Teplow DB, Bowers MT. 66.  2012. Familial Alzheimer's disease mutations differentially alter amyloid β-protein oligomerization. ACS Chem. Neurosci. 3:11909–18 [Google Scholar]
  67. Zheng X, Liu D, Roychaudhuri R, Teplow DB, Bowers MT. 67.  2015. Amyloid β-protein assembly: differential effects of the protective A2T mutation and recessive A2V familial Alzheimer's disease mutation. ACS Chem. Neurosci. 6:101732–40 [Google Scholar]
  68. Bleiholder C, Dupuis NF, Wyttenbach T, Bowers MT. 68.  2011. Ion mobility-mass spectrometry reveals a conformational conversion from random assembly to β-sheet in amyloid fibril formation. Nat. Chem. 3:2172–77 [Google Scholar]
  69. Sawaya MR, Sambashivan S, Nelson R, Ivanova MI, Sievers SA. 69.  et al. 2007. Atomic structures of amyloid cross-β spines reveal varied steric zippers. Nature 447:453–57 [Google Scholar]
  70. Smith GD, Griffin JF. 70.  1978. Conformation of [Leu5] enkephalin from X-ray diffraction: features important for recognition at the opiate receptor. Science 199:1214–16 [Google Scholar]
  71. Trovato A, Chiti F, Maritan A, Seno F. 71.  2006. Insight into the structure of amyloid fibrils from the analysis of globular proteins. PLOS Comput. Biol. 2:12e170 [Google Scholar]
  72. Pawar AP, DuBay KF, Zurdo J, Chiti F, Vendruscolo M, Dobson CM. 72.  2005. Prediction of “aggregation-prone” and “aggregation-susceptible” regions in proteins associated with neurodegenerative diseases. J. Mol. Biol. 350:2379–92 [Google Scholar]
  73. Goldschmidt L, Teng PK, Riek R, Eisenberg D. 73.  2010. Identifying the amylome, proteins capable of forming amyloid-like fibrils. PNAS 107:83487–92 [Google Scholar]
  74. Berman HM, Henrick K, Nakamura H. 74.  2003. Announcing the worldwide Protein Data Bank. Nat. Struct. Biol. 10:980 [Google Scholar]
  75. Do TD, Economou NJ, LaPointe NE, Kincannon WM, Bleiholder C. 75.  et al. 2013. Factors that drive peptide assembly and fibril formation: experimental and theoretical analysis of Sup35 NNQQNY mutants. J. Phys. Chem. B 117:288436–46 [Google Scholar]
  76. Do TD, LaPointe NE, Sangwan S, Teplow DB, Feinstein SC. 76.  et al. 2014. Factors that drive peptide assembly from native to amyloid structures: experimental and theoretical analysis of [Leu-5]-enkephalin mutants. J. Phys. Chem. B 118:267247–56 [Google Scholar]
  77. Liu C, Zhao M, Jiang L, Cheng GN, Park J. 77.  et al. 2012. Out-of-register β-sheets suggest a pathway to toxic amyloid aggregates. PNAS 109:5120913–18 [Google Scholar]
  78. Pike CJ, Walencewicz-Wasserman AJ, Kosmoski J, Cribbs DH, Glabe CG, Cotman CW. 78.  1995. Structure-activity analyses of β-amyloid peptides: contributions of the β25–35 region to aggregation and neurotoxicity. J. Neurochem. 64:253–65 [Google Scholar]
  79. Bleiholder C, Do TD, Wu C. 79.  2013. Ion mobility spectrometry reveals the mechanism of amyloid formation of Aβ(25–35) and its modulation by inhibitors at the molecular level: epigallocatechin gallate and Scyllo-inositol. J. Am. Chem. Soc. 135:4516926–37 [Google Scholar]
  80. Do TD, LaPointe NE, Nelson R, Krotee P, Hayden EY. 80.  et al. 2016. Amyloid β-protein C-terminal fragments: formation of cylindrins and β-barrels. J. Am. Chem. Soc. 138:2549–57 [Google Scholar]
  81. Warnke S, Baldauf C, Bowers MT, Pagel K, von Helden G. 81.  2014. Photodissociation of conformer-selected ubiquitin ions reveals site-specific Cis/Trans isomerization of proline peptide bonds. J. Am. Chem. Soc 136:2910308–14 [Google Scholar]
  82. Seo J, Hoffman W, Warnke S, Huang X Gewinner S. 82.  et al. 2017. An infrared spectroscopy approach to follow β-sheet formation in peptide amyloid assemblies. Nat. Chem. 9:39–44 [Google Scholar]
  83. Koch KJ, Zhang D, Cooks RG, Gozzo FC, Eberlin MN. 83.  2001. Serine octamer metaclusters: formation, structure elucidation and implications for homochiral polymerization. Chem. Commun.181854–55 [Google Scholar]
  84. Cooks RG, Zhang D, Koch KJ, Gozzo FC, Eberlin MN. 84.  2001. Chiroselective self-directed octamerization of serine: implications for homochirogenesis. Anal. Chem. 73:153646–55 [Google Scholar]
  85. Julian RR, Hodyss R, Kinnear B, Jarrold MF, Beauchamp JL. 85.  2002. Nanocrystalline aggregation of serine detected by electrospray ionization mass spectrometry: origin of the stable homochiral gas-phase serine octamer. J. Phys. Chem. B 106:61219–28 [Google Scholar]
  86. Schalley CA, Weis P. 86.  2002. Unusually stable magic number clusters of serine with a surprising preference for homochirality. Int. J. Mass Spectrom. 221:19–19 [Google Scholar]
  87. Spencer EAC, Ly T, Julian RR. 87.  2008. Formation of the serine octamer: Ion evaporation or charge residue?. Int. J. Mass Spectrom. 270:3166–72 [Google Scholar]
  88. Julian RR, Hodyss R, Beauchamp JL. 88.  2001. Salt bridge stabilization of charged zwitterionic arginine aggregates in the gas phase. J. Am. Chem. Soc. 123:153577–83 [Google Scholar]
  89. Feketeová L, Khairallah GN, Brunet C. 89.  2010. Fragmentation of the tryptophan cluster [Trp9–2H]2− induced by different activation methods. Rapid Commun. Mass Spectrom. 24:223255–60 [Google Scholar]
  90. Counterman AE, Clemmer DE. 90.  2004. Anhydrous polyproline helices and globules. J. Phys. Chem. B 108:154885–98 [Google Scholar]
  91. Shaham-Niv S, Adler-Abramovich L, Schnaider L, Gazit E. 91.  2015. Extension of the generic amyloid hypothesis to nonproteinaceous metabolite assemblies. Sci. Adv. 1:7e1500137 [Google Scholar]
  92. Adler-Abramovich L, Vaks L, Carny O. 92.  2012. Phenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria. Nat. Chem. Biol. 8:8701–6 [Google Scholar]
  93. Reches M, Gazit E. 93.  2003. Casting metal nanowires within discrete self-assembled peptide nanotubes. Science 300:625–27 [Google Scholar]
  94. Do TD, Kincannon WM, Bowers MT. 94.  2015. Phenylalanine oligomers and fibrils: the mechanism of assembly and the importance of tetramers and counterions. J. Am. Chem. Soc. 137:3210080–83 [Google Scholar]
  95. German HW, Uyaver S, Hansmann AU. 95.  2015. Self assembly of phenylalanine-based molecules. J. Phys. Chem. A 119:91609–15 [Google Scholar]
  96. Do TD, de Almeida NEC, LaPointe NE, Chamas A, Feinstein SC, Bowers MT. 96.  2016. Amino acid metaclusters: implications of growth trends on peptide self-assembly and structure. Anal. Chem. 88:1868–76 [Google Scholar]
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