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Journal of The American Society for Mass Spectrometry

, Volume 29, Issue 9, pp 1870–1880 | Cite as

Native Top-Down Mass Spectrometry and Ion Mobility MS for Characterizing the Cobalt and Manganese Metal Binding of α-Synuclein Protein

  • Piriya Wongkongkathep
  • Jong Yoon Han
  • Tae Su Choi
  • Sheng Yin
  • Hugh I. Kim
  • Joseph A. Loo
Focus: Application of Photons and Radicals for MS: Research Article

Abstract

Structural characterization of intrinsically disordered proteins (IDPs) has been a major challenge in the field of protein science due to limited capabilities to obtain full-length high-resolution structures. Native ESI-MS with top-down MS was utilized to obtain structural features of protein-ligand binding for the Parkinson’s disease-related protein, α-synuclein (αSyn), which is natively unstructured. Binding of heavy metals has been implicated in the accelerated formation of αSyn aggregation. Using high-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry, native top-down MS with various fragmentation methods, including electron capture dissociation (ECD), collisional activated dissociation (CAD), and multistage tandem MS (MS3), deduced the binding sites of cobalt and manganese to the C-terminal region of the protein. Ion mobility MS (IM-MS) revealed a collapse toward compacted states of αSyn upon metal binding. The combination of native top-down MS and IM-MS provides structural information of protein-ligand interactions for intrinsically disordered proteins.

Graphical Abstract

Keywords

Native mass spectrometry α-Synuclein Metal binding Protein-ligand complex Top-down mass spectrometry Electron capture dissociation Electrospray ionization 

Notes

Funding Information

This study received support from the US National Institutes of Health (R01GM103479, S10RR028893, S10OD018504 to J.A.L.); the US Department of Energy (DE-FC02-02ER63421 to J.A.L.); the Development and Promotion of Science and Technology Talents Project (DPST) and Royal Thai Government (to P.W.); the Rachadapisek Sompot Fund, Chulalongkorn University (to P.W.); the National Research Foundation of Korea (NRF) (NRF-2016R1A2B4013089 and 20100020209 to H.I.K.); Korea University Future Research Grant (to H.I.K.); and the Ministry of Science, ICT and Future Planning (CAP-15-10-KRICT to H.I.K.).

Supplementary material

13361_2018_2002_MOESM1_ESM.pdf (328 kb)
ESM 1 (PDF 327 kb)

References

  1. 1.
    Polymeropoulos, M.H., Lavedan, C., Leroy, E., Ide, S.E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., Stenroos, E.S., Chandrasekharappa, S., Athanassiadou, A., Papapetropoulos, T., Johnson, W.G., Lazzarini, A.M., Duvoisin, R.C., Di Iorio, G., Golbe, L.I., Nussbaum, R.L.: Mutation in the α-synuclein gene identified in families with Parkinson’s disease. Science. 276, 2045–2047 (1997)CrossRefGoogle Scholar
  2. 2.
    Mezey, E., Dehejia, A.M., Harta, G., Suchy, S.F., Nussbaum, R.L., Brownstein, M.J., Polymeropoulos, M.H.: Alpha synuclein is present in lewy bodies in sporadic Parkinson’s disease. Mol. Psych. 3, 493 (1998)CrossRefGoogle Scholar
  3. 3.
    Singleton, A.B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., Nussbaum, R., Lincoln, S., Crawley, A., Hanson, M., Maraganore, D., Adler, C., Cookson, M.R., Muenter, M., Baptista, M., Miller, D., Blancato, J., Hardy, J., Gwinn-Hardy, K.: α-Synuclein locus triplication causes Parkinson’s disease. Science. 302, 841–841 (2003)CrossRefGoogle Scholar
  4. 4.
    Spillantini, M.G., Schmidt, M.L., Lee, V.M.Y., Trojanowski, J.Q., Jakes, R., Goedert, M.: α-Synuclein in Lewy bodies. Nature. 388, 839–840 (1997)CrossRefGoogle Scholar
  5. 5.
    Mukaetova-Ladinska, E.B., McKeith, I.G.: Pathophysiology of synuclein aggregation in Lewy body disease. Mech. Ageing Dev. 127, 188–202 (2006)CrossRefGoogle Scholar
  6. 6.
    Grazia Spillantini, M., Anthony Crowther, R., Jakes, R., Cairns, N.J., Lantos, P.L., Goedert, M.: Filamentous α-synuclein inclusions link multiple system atrophy with Parkinson’s disease and dementia with lewy bodies. Neurosci. Lett. 251, 205–208 (1998)CrossRefGoogle Scholar
  7. 7.
    Wakabayashi, K., Yoshimoto, M., Tsuji, S., Takahashi, H.: α-Synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neurosci. Lett. 249, 180–182 (1998)CrossRefGoogle Scholar
  8. 8.
    Lee, S.J.C., Lee, J.W., Choi, T.S., Jin, K.S., Lee, S., Ban, C., Kim, H.I.: Probing conformational change of intrinsically disordered α-synuclein to helical structures by distinctive regional interactions with lipid membranes. Anal. Chem. 86, 1909–1916 (2014)CrossRefGoogle Scholar
  9. 9.
    Ulmer, T.S., Bax, A.: Comparison of structure and dynamics of micelle-bound human α-synuclein and Parkinson disease variants. J. Biol. Chem. 280, 43179–43187 (2005)CrossRefGoogle Scholar
  10. 10.
    Burré, J., Sharma, M., Tsetsenis, T., Buchman, V., Etherton, M.R., Südhof, T.C.: α-Synuclein promotes snare-complex assembly in vivo and in vitro. Science. 329, 1663–1667 (2010)CrossRefGoogle Scholar
  11. 11.
    Masliah, E., Rockenstein, E., Veinbergs, I., Mallory, M., Hashimoto, M., Takeda, A., Sagara, Y., Sisk, A., Mucke, L.: Dopaminergic loss and inclusion body formation in α-synuclein mice: implications for neurodegenerative disorders. Science. 287, 1265–1269 (2000)CrossRefGoogle Scholar
  12. 12.
    Perez, R.G., Waymire, J.C., Lin, E., Liu, J.J., Guo, F., Zigmond, M.J.: A role for α-synuclein in the regulation of dopamine biosynthesis. J. Neurosci. 22, 3090–3099 (2002)CrossRefGoogle Scholar
  13. 13.
    Sidhu, A., Wersinger, C., Vernier, P.: Α-synuclein regulation of the dopaminergic transporter: a possible role in the pathogenesis of Parkinson’s disease. FEBS Lett. 565, 1–5 (2004)CrossRefGoogle Scholar
  14. 14.
    Illes-Toth, E., Dalton, C.F., Smith, D.P.: Binding of dopamine to alpha-synuclein is mediated by specific conformational states. J. Am. Soc. Mass Spectrom. 24, 1346–1354 (2013)CrossRefGoogle Scholar
  15. 15.
    Uversky, V.N., Li, J., Fink, A.L.: Evidence for a partially folded intermediate in α-synuclein fibril formation. J. Biol. Chem. 276, 10737–10744 (2001)CrossRefGoogle Scholar
  16. 16.
    Uversky, V.N.: A protein-chameleon: conformational plasticity of alpha-synuclein, a disordered protein involved in neurodegenerative disorders. J. Biomol. Struct. Dyn. 21, 211–234 (2003)CrossRefGoogle Scholar
  17. 17.
    Sung, Y.-h., Eliezer, D.: Residual structure, backbone dynamics, and interactions within the synuclein family. J. Mol. Biol. 372, 689–707 (2007)CrossRefGoogle Scholar
  18. 18.
    Zhao, M., Cascio, D., Sawaya, M.R., Eisenberg, D.: Structures of segments of α-synuclein fused to maltose-binding protein suggest intermediate states during amyloid formation. Protein Sci. 20, 996–1004 (2011)CrossRefGoogle Scholar
  19. 19.
    Rodriguez, J.A., Ivanova, M.I., Sawaya, M.R., Cascio, D., Reyes, F.E., Shi, D., Sangwan, S., Guenther, E.L., Johnson, L.M., Zhang, M., Jiang, L., Arbing, M.A., Nannenga, B.L., Hattne, J., Whitelegge, J., Brewster, A.S., Messerschmidt, M., Boutet, S., Sauter, N.K., Gonen, T., Eisenberg, D.S.: Structure of the toxic core of α-synuclein from invisible crystals. Nature. 525, 486–490 (2015)CrossRefGoogle Scholar
  20. 20.
    Heise, H., Hoyer, W., Becker, S., Andronesi, O.C., Riedel, D., Baldus, M.: Molecular-level secondary structure, polymorphism, and dynamics of full-length α-synuclein fibrils studied by solid-state NMR. Proc. Natl. Acad. Sci. U. S. A. 102, 15871–15876 (2005)CrossRefGoogle Scholar
  21. 21.
    Vilar, M., Chou, H.-T., Lührs, T., Maji, S.K., Riek-Loher, D., Verel, R., Manning, G., Stahlberg, H., Riek, R.: The fold of α-synuclein fibrils. Proc. Natl. Acad. Sci. U. S. A. 105, 8637–8642 (2008)CrossRefGoogle Scholar
  22. 22.
    Jao, C.C., Der-Sarkissian, A., Chen, J., Langen, R.: Structure of membrane-bound α-synuclein studied by site-directed spin labeling. Proc. Natl. Acad. Sci. U. S. A. 101, 8331–8336 (2004)CrossRefGoogle Scholar
  23. 23.
    Chen, M., Margittai, M., Chen, J., Langen, R.: Investigation of α-synuclein fibril structure by site-directed spin labeling. J. Biol. Chem. 282, 24970–24979 (2007)CrossRefGoogle Scholar
  24. 24.
    Li, J., Uversky, V.N., Fink, A.L.: Conformational behavior of human α-synuclein is modulated by familial parkinson’s disease point mutations A30P and A53T. Neurotoxicol. 23, 553–567 (2002)CrossRefGoogle Scholar
  25. 25.
    Bernado, P., Svergun, D.I.: Structural analysis of intrinsically disordered proteins by small-angle x-ray scattering. Mol. BioSys. 8, 151–167 (2012)CrossRefGoogle Scholar
  26. 26.
    Beyer, K.: α-Synuclein structure, posttranslational modification and alternative splicing as aggregation enhancers. Acta Neuropathol. 112, 237–251 (2006)CrossRefGoogle Scholar
  27. 27.
    Bisaglia, M., Mammi, S., Bubacco, L.: Structural insights on physiological functions and pathological effects of α-synuclein. FASEB J. 23, 329–340 (2009)CrossRefGoogle Scholar
  28. 28.
    Bartels, T., Choi, J.G., Selkoe, D.J.: α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature. 477, 107–110 (2011)CrossRefGoogle Scholar
  29. 29.
    Bartels, T., Kim, N.C., Luth, E.S., Selkoe, D.J.: N-alpha-acetylation of α-synuclein increases its helical folding propensity, GM1 binding specificity and resistance to aggregation. PLoS One. 9, e103727 (2014)CrossRefGoogle Scholar
  30. 30.
    Maltsev, A.S., Ying, J., Bax, A.: Impact of N-terminal acetylation of α-synuclein on its random coil and lipid binding properties. Biochemistry. 51, 5004–5013 (2012)CrossRefGoogle Scholar
  31. 31.
    Burré, J., Sharma, M., Südhof, T.C.: α-Synuclein assembles into higher-order multimers upon membrane binding to promote snare complex formation. Proc. Natl. Acad. Sci. U. S. A. 111, E4274–E4283 (2014)CrossRefGoogle Scholar
  32. 32.
    Bodles, A.M., Guthrie, D.J.S., Greer, B., Irvine, G.B.: Identification of the region of non-aβ component (NAC) of Alzheimer’s disease amyloid responsible for its aggregation and toxicity. J. Neurochem. 78, 384–395 (2001)CrossRefGoogle Scholar
  33. 33.
    Ehrnhoefer, D.E., Bieschke, J., Boeddrich, A., Herbst, M., Masino, L., Lurz, R., Engemann, S., Pastore, A., Wanker, E.E.: EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Nat. Struct. Mol. Biol. 15, 558–566 (2008)CrossRefGoogle Scholar
  34. 34.
    Ahmad, A., Burns, C.S., Fink, A.L., Uversky, V.N.: Peculiarities of copper binding to alpha-synuclein. J. Biomol. Struct. Dyn. 29, 825–842 (2012)CrossRefGoogle Scholar
  35. 35.
    Singh, P.K., Kotia, V., Ghosh, D., Mohite, G.M., Kumar, A., Maji, S.K.: Curcumin modulates alpha-synuclein aggregation and toxicity. ACS Chem. Neurosci. 4, 393–407 (2013)CrossRefGoogle Scholar
  36. 36.
    Bernstein, S.L., Liu, D., Wyttenbach, T., Bowers, M.T., Lee, J.C., Gray, H.B., Winkler, J.R.: α-Synuclein: stable compact and extended monomeric structures and ph dependence of dimer formation. J. Am. Soc. Mass Spectrom. 15, 1435–1443 (2004)CrossRefGoogle Scholar
  37. 37.
    Tucker, W.C., Edwardson, J.M., Bai, J., Kim, H.J., Martin, T.F., Chapman, E.R.: Identification of synaptotagmin effectors via acute inhibition of secretion from cracked PC12 cells. J. Cell Biol. 162, 199–209 (2003)CrossRefGoogle Scholar
  38. 38.
    Prabhudesai, S., Sinha, S., Attar, A., Kotagiri, A., Fitzmaurice, A.G., Lakshmanan, R., Ivanova, M.I., Loo, J.A., Klarner, F.G., Schrader, T., Stahl, M., Bitan, G., Bronstein, J.M.: A novel “molecular tweezer” inhibitor of α-synuclein neurotoxicity in vitro and in vivo. Neurotherapeutics. 9, 464–476 (2012)CrossRefGoogle Scholar
  39. 39.
    Acharya, S., Safaie, B.M., Wongkongkathep, P., Ivanova, M.I., Attar, A., Klärner, F.-G., Schrader, T., Loo, J.A., Bitan, G., Lapidus, L.J.: Molecular basis for preventing α-synuclein aggregation by a molecular tweezer. J. Biol. Chem. 289, 10727–10737 (2014)CrossRefGoogle Scholar
  40. 40.
    Uversky, V.N., Li, J., Fink, A.L.: Metal-triggered structural transformations, aggregation, and fibrillation of human α-synuclein. A possible molecular link between Parkinson’s disease and heavy metal exposure. J. Biol. Chem. 276, 44284–44296 (2001)CrossRefGoogle Scholar
  41. 41.
    Binolfi, A., Rasia, R.M., Bertoncini, C.W., Ceolin, M., Zweckstetter, M., Griesinger, C., Jovin, T.M., Fernández, C.O.: Interaction of α-synuclein with divalent metal ions reveals key differences: a link between structure, binding specificity and fibrillation enhancement. J. Am. Chem. Soc. 128, 9893–9901 (2006)CrossRefGoogle Scholar
  42. 42.
    Brown, D.R.: Metal binding to alpha-synuclein peptides and its contribution to toxicity. Biochem. Biophys. Res. Commun. 380, 377–381 (2009)CrossRefGoogle Scholar
  43. 43.
    Natalello, A., Benetti, F., Doglia, S.M., Legname, G., Grandori, R.: Compact conformations of α-synuclein induced by alcohols and copper. Proteins. 79, 611–621 (2011)CrossRefGoogle Scholar
  44. 44.
    Rasia, R.M., Bertoncini, C.W., Marsh, D., Hoyer, W., Cherny, D., Zweckstetter, M., Griesinger, C., Jovin, T.M., Fernandez, C.O.: Structural characterization of copper(II) binding to α-synuclein: insights into the bioinorganic chemistry of Parkinson’s disease. Proc. Natl. Acad. Sci. U. S. A. 102, 4294–4299 (2005)CrossRefGoogle Scholar
  45. 45.
    Sung, Y.H., Rospigliosi, C., Eliezer, D.: Nmr mapping of copper binding sites in alpha-synuclein. Biochim. Biophys. Acta. 1764, 5–12 (2006)CrossRefGoogle Scholar
  46. 46.
    Bharathi, Rao, K.S.: Molecular understanding of copper and iron interaction with α-synuclein by fluorescence analysis. J. Mol. Neurosci. 35, 273–281 (2008)CrossRefGoogle Scholar
  47. 47.
    Binolfi, A., Lamberto, G.R., Duran, R., Quintanar, L., Bertoncini, C.W., Souza, J.M., Cerveñansky, C., Zweckstetter, M., Griesinger, C., Fernández, C.O.: Site-specific interactions of Cu(II) with α and β-synuclein: bridging the molecular gap between metal binding and aggregation. J. Am. Chem. Soc. 130, 11801–11812 (2008)CrossRefGoogle Scholar
  48. 48.
    Dudzik, C.G., Walter, E.D., Millhauser, G.L.: Coordination features and affinity of the Cu2+ site in the α-synuclein protein of Parkinson’s disease. Biochemistry. 50, 1771–1777 (2011)CrossRefGoogle Scholar
  49. 49.
    Dudzik, C.G., Walter, E.D., Abrams, B.S., Jurica, M.S., Millhauser, G.L.: Coordination of copper to the membrane-bound form of α-synuclein. Biochemistry. 52, 53–60 (2013)CrossRefGoogle Scholar
  50. 50.
    Moriarty, G.M., Minetti, C.A., Remeta, D.P., Baum, J.: A revised picture of the cu(II)−α-synuclein complex: the role of N-terminal acetylation. Biochemistry. 53, 2815–2817 (2014)CrossRefGoogle Scholar
  51. 51.
    Aaron, S., Vladimir, N.U.: α-Synuclein and metals. In: Gomes, C.M., Wittung-Stafshede, P. (eds.) Protein folding and metal ions, pp. 169-191. CRC Press, Boca Raton (2010)Google Scholar
  52. 52.
    Andrés, B., Claudio, O.F.: Interactions of α-synuclein with metal ions. In: Brown, D.R. (ed.) Brain diseases and metalloproteins, pp. 327-366. Pan Stanford Publishing, Singapore (2012)Google Scholar
  53. 53.
    Binolfi, A., Quintanar, L., Bertoncini, C.W., Griesinger, C., Fernández, C.O.: Bioinorganic chemistry of copper coordination to alpha-synuclein: relevance to Parkinson’s disease. Coord. Chem. Rev. 256, 2188–2201 (2012)CrossRefGoogle Scholar
  54. 54.
    Han, X., Jin, M., Breuker, K., McLafferty, F.W.: Extending top-down mass spectrometry to proteins with masses greater than 200 kiloDaltons. Science. 314, 109–112 (2006)CrossRefGoogle Scholar
  55. 55.
    Xie, Y., Zhang, J., Yin, S., Loo, J.A.: Top-down ESI-ECD-FT-ICR mass spectrometry localizes noncovalent protein-ligand binding sites. J. Am. Chem. Soc. 128, 14432–14433 (2006)CrossRefGoogle Scholar
  56. 56.
    Li, H., Wolff, J.J., Van Orden, S.L., Loo, J.A.: Native top-down electrospray ionization-mass spectrometry of 158 kDa protein complex by high-resolution Fourier transform ion cyclotron resonance mass spectrometry. Anal. Chem. 86, 317–320 (2014)CrossRefGoogle Scholar
  57. 57.
    Li, H., Wongkongkathep, P., Van Orden, S.L., Ogorzalek Loo, R.R., Loo, J.A.: Revealing ligand binding sites and quantifying subunit variants of noncovalent protein complexes in a single native top-down FTICR MS experiment. J. Am. Soc. Mass Spectrom. 25, 2060–2068 (2014)CrossRefGoogle Scholar
  58. 58.
    Li, H., Nguyen, H.H., Ogorzalek-Loo, R.R., Campuzano, I.D.G., Loo, J.A.: An integrated native mass spectrometry and top-down proteomics method that connects sequence to structure and function of macromolecular complexes. Nat. Chem. 10, 139–148 (2018)CrossRefGoogle Scholar
  59. 59.
    Yin, S., Loo, J.A.: Top-down mass spectrometry of supercharged native protein-ligand complexes. Int. J. Mass Spectrom. 300, 118–122 (2011)CrossRefGoogle Scholar
  60. 60.
    Woods, A.S., Ferré, S.: Amazing stability of the arginine−phosphate electrostatic interaction. J. Proteome Res. 4, 1397–1402 (2005)CrossRefGoogle Scholar
  61. 61.
    Bartman, C.E., Metwally, H., Konermann, L.: Effects of multidentate metal interactions on the structure of collisionally activated proteins: insights from ion mobility spectrometry and molecular dynamics simulations. Anal. Chem. 88, 6905–6913 (2016)CrossRefGoogle Scholar
  62. 62.
    Yin, S., Xie, Y., Loo, J.A.: Mass spectrometry of protein-ligand complexes: enhanced gas-phase stability of ribonuclease-nucleotide complexes. J. Am. Soc. Mass Spectrom. 19, 1199–1208 (2008)CrossRefGoogle Scholar
  63. 63.
    Yin, S., Loo, J.A.: Elucidating the site of protein-ATP binding by top-down mass spectrometry. J. Am. Soc. Mass Spectrom. 21, 899–907 (2010)CrossRefGoogle Scholar
  64. 64.
    Wyttenbach, T., Pierson, N.A., Clemmer, D.E., Bowers, M.T.: Ion mobility analysis of molecular dynamics. Ann. Rev. Phys. Chem. 65, 175–196 (2014)CrossRefGoogle Scholar
  65. 65.
    Loo, J.A., Edmonds, C.G., Smith, R.D.: Primary sequence information from intact proteins by electrospray ionization tandem mass spectrometry. Science. 248, 201–204 (1990)CrossRefGoogle Scholar
  66. 66.
    Ruotolo, B.T., Benesch, J.L.P., Sandercock, A.M., Hyung, S.-J., Robinson, C.V.: Ion mobility-mass spectrometry analysis of large protein complexes. Nat. Protocols. 3, 1139–1152 (2008)CrossRefGoogle Scholar
  67. 67.
    Bush, M.F., Hall, Z., Giles, K., Hoyes, J., Robinson, C.V., Ruotolo, B.T.: Collision cross sections of proteins and their complexes: a calibration framework and database for gas-phase structural biology. Anal. Chem. 82, 9557–9565 (2010)CrossRefGoogle Scholar
  68. 68.
    Schwartz, B.L., Bursey, M.M.: Some proline substituent effects in the tandem mass spectrum of protonated pentaalanine. Biol. Mass Spectrom. 21, 92–96 (1992)CrossRefGoogle Scholar
  69. 69.
    Light-Wahl, K.J., Loo, J.A., Edmonds, C.G., Smith, R.D., Witkowska, H.E., Shackleton, C.H.L., Wu, C.S.C.: Tandem mass spectrometry of intact hemoglobin variant proteins with electrospray ionization. Biol. Mass Spectrom. 22, 112–120 (1993)CrossRefGoogle Scholar
  70. 70.
    Yu, W., Vath, J.E., Huberty, M.C., Martin, S.A.: Identification of the facile gas-phase cleavage of the Asp-Pro and Asp-xxx peptide bonds in matrix-assisted laser desorption time-of-flight mass spectrometry. Anal. Chem. 65, 3015–3023 (1993)CrossRefGoogle Scholar
  71. 71.
    Chanthamontri, C., Liu, J., McLuckey, S.A.: Charge state dependent fragmentation of gaseous α-synuclein cations via ion trap and beam-type collisional activation. Int. J. Mass Spectrom. 283, 9–16 (2009)CrossRefGoogle Scholar
  72. 72.
    Ogorzalek Loo, R.R., Lakshmanan, R., Loo, J.A.: What protein charging (and supercharging) reveal about the mechanism of electrospray ionization. J. Am. Soc. Mass Spectrom. 25, 1675–1693 (2014)CrossRefGoogle Scholar
  73. 73.
    Hall, Z., Robinson, C.V.: Do charge state signatures guarantee protein conformations? J. Am. Soc. Mass Spectrom. 23, 1161–1168 (2012)CrossRefGoogle Scholar
  74. 74.
    Kaltashov, I.A., Abzalimov, R.R.: Do ionic charges in ESI MS provide useful information on macromolecular structure? J. Am. Soc. Mass Spectrom. 19, 1239–1246 (2008)CrossRefGoogle Scholar
  75. 75.
    Hamdy, O.M., Julian, R.R.: Reflections on charge state distributions, protein structure, and the mystical mechanism of electrospray ionization. J. Am. Soc. Mass Spectrom. 23, 1–6 (2012)CrossRefGoogle Scholar
  76. 76.
    Zhou, M., Politis, A., Davies, R.B., Liko, I., Wu, K.-J., Stewart, A.G., Stock, D., Robinson, C.V.: Ion mobility–mass spectrometry of a rotary ATPase reveals ATP-induced reduction in conformational flexibility. Nat. Chem. 6, 208–215 (2014)CrossRefGoogle Scholar
  77. 77.
    Lanucara, F., Holman, S.W., Gray, C.J., Eyers, C.E.: The power of ion mobility-mass spectrometry for structural characterization and the study of conformational dynamics. Nat. Chem. 6, 281–294 (2014)CrossRefGoogle Scholar
  78. 78.
    Laganowsky, A., Reading, E., Allison, T.M., Ulmschneider, M.B., Degiacomi, M.T., Baldwin, A.J., Robinson, C.V.: Membrane proteins bind lipids selectively to modulate their structure and function. Nature. 510, 172–175 (2014)CrossRefGoogle Scholar
  79. 79.
    Hall, Z., Politis, A., Bush, M.F., Smith, L.J., Robinson, C.V.: Charge-state dependent compaction and dissociation of protein complexes: insights from ion mobility and molecular dynamics. J. Am. Chem. Soc. 134, 3429–3438 (2012)CrossRefGoogle Scholar
  80. 80.
    Hyung, S.-J., Robinson, C.V., Ruotolo, B.T.: Gas-phase unfolding and disassembly reveals stability differences in ligand-bound multiprotein complexes. Chem. Biol. 16, 382–390 (2009)CrossRefGoogle Scholar
  81. 81.
    Choi, T.S., Lee, J., Han, J.Y., Jung, B.C., Wongkongkathep, P., Loo, J.A., Lee, M.J., Kim, H.I.: Supramolecular modulation of structural polymorphism in pathogenic α-synuclein fibrils using copper(II) coordination. Angew. Chem. Int. Ed. 57, 3099–3103 (2018)CrossRefGoogle Scholar
  82. 82.
    Zhou, M., Yan, J., Romano, C.A., Tebo, B.M., Wysocki, V.H., Paša-Tolić, L.: Surface induced dissociation coupled with high resolution mass spectrometry unveils heterogeneity of a 211 kDa multicopper oxidase protein complex. J. Am. Soc. Mass Spectrom. 29, 723–733 (2018)CrossRefGoogle Scholar
  83. 83.
    O’Brien, J.P., Li, W., Zhang, Y., Brodbelt, J.S.: Characterization of native protein complexes using ultraviolet photodissociation mass spectrometry. J. Am. Chem. Soc. 136, 12920–12928 (2014)CrossRefGoogle Scholar
  84. 84.
    Li, H., Sheng, Y., McGee, W., Cammarata, M., Holden, D., Loo, J.A.: Structural characterization of native proteins and protein complexes by electron ionization dissociation-mass spectrometry. Anal. Chem. 89, 2731–2738 (2017)CrossRefGoogle Scholar

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© American Society for Mass Spectrometry 2018

Authors and Affiliations

  1. 1.Department of Chemistry and BiochemistryUniversity of California-Los AngelesLos AngelesUSA
  2. 2.Center of Excellence in Systems Biology, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  3. 3.Department of ChemistryKorea UniversitySeoulRepublic of Korea
  4. 4.Department of Biological Chemistry, David Geffen School of Medicine at UCLA, UCLA Molecular Biology Institute, and UCLA/DOE Institute for Genomics and ProteomicsUniversity of California-Los AngelesLos AngelesUSA

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