Monitoring copopulated conformational states during protein folding events using electrospray ionization-ion mobility spectrometry-mass spectrometry
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- 作者：David P. Smith (1)
Kevin Giles (2)
Robert H. Bateman (2)
Sheena E. Radford (1)
Alison E. Ashcroft (1) - 刊名：Journal of The American Society for Mass Spectrometry
- 出版年：2007
- 出版时间：December 2007
- 年：2007
- 卷：18
- 期：12
- 页码：2180-2190
- 全文大小：901KB
- 参考文献：1. Barral, J. M.; Broadley, S. A.; Schaffar, G.; Hartl, F. U. Roles of molecular chaperone in protein misfolding diseases. / Semin. Cell Dev. Biol. plus-plus">2004, / 15, 17-9. p://dx.doi.org/10.1016/j.semcdb.2003.12.010">CrossRef
2. Lindberg, M. O.; Oliveberg, M. Malleability of protein folding pathways: A simple reason for complex behavior. / Curr. Opin. Struct. Biol. plus-plus">2007, / 17, 21-9. p://dx.doi.org/10.1016/j.sbi.2007.01.008">CrossRef
3. Brockwell, D. J.; Radford, S. E. Intermediates: Ubiquitous species on folding energy landscapes? / Curr. Opin. Struct. Biol. plus-plus">2007, / 17, 30-7. p://dx.doi.org/10.1016/j.sbi.2007.01.003">CrossRef
4. Dobson, C. M. Protein folding and misfolding. / Nature plus-plus">2003, / 426, 884-90. p://dx.doi.org/10.1038/nature02261">CrossRef
5. Kelly, J. W. Towards an understanding of amyloidogenesis. / Nature Struct. Biol. plus-plus">2002, / 9, 323-25. p://dx.doi.org/10.1038/nsb0502-323">CrossRef
6. Chiti, F.; Dobson, C. M. Protein misfolding, functional amyloid, and human disease. / Annu. Rev. Biochem. plus-plus">2006, / 75, 333-66. p://dx.doi.org/10.1146/annurev.biochem.75.101304.123901">CrossRef
7. Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Electrospray ionization for mass spectrometry of large biomolecules. / Science plus-plus">1989, / 246, 64-1. p://dx.doi.org/10.1126/science.2675315">CrossRef
8. Kaltashov, I. A.; Eyles, S. J. Studies of biomolecular conformations and conformational dynamics by mass spectrometry. / Mass Spectrom. Rev. plus-plus">2002, / 21, 37-1. p://dx.doi.org/10.1002/mas.10017">CrossRef
9. Ashcroft, A. E.; Brinker, A.; Coyle, J. E.; Weber, F.; Kaiser, M.; Moroder, L.; Parsons, M. R.; Jaeger, J.; Hartl, U. F.; Hayer-Hartl, M.; Radford, S. E. Structural plasticity and noncovalent substrate binding in the GroEL apical domain: A study using electrospray ionization mass spectrometry and fluorescence binding studies. / J. Biol. Chem. plus-plus">2002, / 277, 33115-3126. p://dx.doi.org/10.1074/jbc.M203398200">CrossRef
10. Loo, J. A.; Loo, R. R.; Usdeth, H. R.; Edmonds, C. G.; Smith, R. D. Solvent induced conformational changes of polypeptides probed by ESI-MS. / Rapid Commun. Mass Spectrom. plus-plus">1991, / 5, 101-05. p://dx.doi.org/10.1002/rcm.1290050303">CrossRef
11. Konermann, L.; Douglas, D. J. Equilibrium unfolding of proteins monitored by electrospray ionization mass spectrometry: Distinguishing two-state from multi-state transitions. / Rapid Commun. Mass Spectrom. plus-plus">1998, / 12, 435-42. p://dx.doi.org/10.1002/(SICI)1097-0231(19980430)12:8<435::AID-RCM181>3.0.CO;2-F">CrossRef
12. Konermann, L.; Silva, E. A.; Sogbein, O. F. Electrochemically induced pH changes resulting in protein unfolding in the ion source of an electrospray mass spectrometer. / Anal. Chem. plus-plus">2001, / 73, 4836-844. p://dx.doi.org/10.1021/ac010545r">CrossRef
13. Dobo, A.; Kaltashov, I. A. Detection of multiple protein conformational ensembles in solution via deconvolution of charge-state distributions in ESI MS. / Anal. Chem. plus-plus">2001, / 73, 4763-773. p://dx.doi.org/10.1021/ac010713f">CrossRef
14. Borysik, A. J. H.; Radford, S. E.; Ashcroft, A. E. Copopulated conformational ensembles of / β plus-plus">2-microglobulin uncovered quantitatively by ESI-MS. / J. Biol. Chem. plus-plus">2004, / 279, 27069-7077. p://dx.doi.org/10.1074/jbc.M401472200">CrossRef
15. Verbeck, G. F.; Ruotolo, B. T.; Sawyer, H. A.; Gillig, K. J.; Russell, D. H. A fundamental introduction to ion mobility mass spectrometry applied to the analysis of biomolecules. / J. Biomol. Techniques. plus-plus">2002, / 13, 56-1.
16. Creaser, C. S.; Griffiths, J. R.; Bramwell, C. J.; Noreen, S.; Hill, C. A.; Thomas, C. L. P. Ion mobility spectrometry: A review: Part I. Structural analysis by mobility measurement. / Analyst plus-plus">2004, / 129, 1658-661. p://dx.doi.org/10.1039/b404531a">CrossRef
17. Hoaglund-Hyzer, C. S.; Counterman, A. E.; Clemmer, D. E. Anhydrous protein ions. / Chem. Rev. plus-plus">1999, / 99, 3037-079. p://dx.doi.org/10.1021/cr980139g">CrossRef
18. Purves, R. W.; Barnett, D. A.; Ells, B.; Guevremont, R. Investigation of bovine ubiquitin conformers separated by high-field asymmetric waveform ion mobility spectrometry: Cross section measurements using energy loss experiments with a triple quadrupole mass spectrometer. / J. Am. Soc. Mass Spectrom. plus-plus">2000, / 11, 738-45. p://dx.doi.org/10.1016/S1044-0305(00)00136-7">CrossRef
19. Pringle, S. D.; Giles, K.; Wildgoose, J. L.; Williams, J. P.; Slade, S. E.; Thalassinos, K.; Bateman, R. H.; Bowers, M. T.; Scrivens, J. H. 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. plus-plus">2007, / 261, 1-2. p://dx.doi.org/10.1016/j.ijms.2006.07.021">CrossRef
20. Giles, K.; Pringle, S. D.; Worthington, K. R.; Little, D. R.; Wildgoose, J. L.; Bateman, R. H. Applications of a traveling wave-based radio-frequency-only stacked ring ion guide. / Rapid Commun. Mass Spectrom. plus-plus">2004, / 18, 2401-414. p://dx.doi.org/10.1002/rcm.1641">CrossRef
21. Ruotolo, B.; Giles, K.; Campuzano, I.; Sandercock, A. M.; Bateman, R. H.; Robinson, C. V. Evidence for macromolecular protein rings in the absence of bulk water. / Science plus-plus">2005, / 310, 1658-661. p://dx.doi.org/10.1126/science.1120177">CrossRef
22. Chowdhury, S. K.; Katta, V.; Chait, B. T. Probing conformational changes in proteins by mass spectrometry. / J. Am. Chem. Soc. plus-plus">1990, / 112, 9012-013. p://dx.doi.org/10.1021/ja00180a074">CrossRef
23. Konermann, L.; Collings, B. A.; Douglas, D. J. Cytochrome / c folding kinetics studied by time-resolved electrospray ionization mass spectrometry. / Biochemistry plus-plus">1997, / 36, 5554-559. p://dx.doi.org/10.1021/bi970046d">CrossRef
24. Grandori, R. Detecting equilibrium cytochrome / c folding intermediates by electrospray ionization mass spectrometry: Two partially folded forms populate the molten globule state. / Prot. Sci. plus-plus">2002, / 11, 453-58. p://dx.doi.org/10.1110/ps.45102">CrossRef
25. Goto, Y.; Hagihara, Y.; Hamada, D.; Hoshino, M.; Nishii, I. Acid-induced unfolding and refolding transitions of cytochrome / c: A three state mechanism in Hplus-plus">2O and Dplus-plus">2O. / Biochem. plus-plus">1993, / 32, 11878-1885. p://dx.doi.org/10.1021/bi00095a017">CrossRef
26. Badman, E. R.; Hoaglund-Hyzer, C. S.; Clemmer, D. E. Monitoring structural changes of proteins in an ion trap over ?00 to 200 ms: Unfolding transitions in cytochrome / c ions. / Anal. Chem. plus-plus">2001, / 73, 6000-007. p://dx.doi.org/10.1021/ac010744a">CrossRef
27. Mao, Y.; Woenckhaus, J.; Kolafa, J.; Ratner, M. A.; Jarrold, M. F. Thermal unfolding of unsolvated cytochrome / c: Experiment and molecular dynamics simulations. / J. Am. Chem. Soc. plus-plus">1999, / 121, 2712-721. p://dx.doi.org/10.1021/ja980324b">CrossRef
28. Jones, S.; Smith, D. P.; Radford, S. E. Role of the N-and C-terminal strands of / β plus-plus">2-microglobulin in amyloid formation at neutral pH. / J. Mol. Biol. plus-plus">2003, / 330, 935-41. p://dx.doi.org/10.1016/S0022-2836(03)00688-0">CrossRef
29. Kad, N. M.; Thomson, N. H.; Smith, D. P.; Smith, D. A.; Radford, S. E. / β plus-plus">2-Microglobulin and its deamidated variant, N17D form amyloid fibrils with a range of morphologies in vitro. / J. Mol. Biol. plus-plus">2001, / 313, 559-71. p://dx.doi.org/10.1006/jmbi.2001.5071">CrossRef
30. Kad, N. M.; Radford, S. E. Partial unfolding as a precursor of amyloidosis: A discussion of the occurrence, role, and implications; In / Molecular chaperones in the cell; Lund, P., Ed.; Oxford University Press: Oxford, UK, 2001; pp. 257-78.
31. McParland, V. J.; Kad, N. M.; Kalverda, A. P.; Brown, A.; Kirwin-Jones, P.; Hunter, M. G.; Sunde, M.; Radford, S. E. Partially unfolded states of / β plus-plus">2-microglobulin and amyloid formation in vitro. / Biochemistry plus-plus">2000, / 39, 8735-746. p://dx.doi.org/10.1021/bi000276j">CrossRef
32. McParland, V. J.; Kalverda, A. P.; Homans, S. W.; Radford, S. E. Structural properties of an amyloid precursor of / β plus-plus">2-microglobulin. / Nat. Struct. Biol. plus-plus">2002, / 5, 326-31. p://dx.doi.org/10.1038/nsb791">CrossRef
33. Smith, D. P.; Jones, S.; Serpell, L. C.; Sunde, M.; Radford, S. E. A systematic investigation into the role of protein destabilization in / β plus-plus">2-microglobulin amyloidosis. / J. Mol. Biol. plus-plus">2003, / 330, 943-54. p://dx.doi.org/10.1016/S0022-2836(03)00687-9">CrossRef
34. Myers, S. L.; Thomson, N. H.; Radford, S. E.; Ashcroft, A. E. Investigating the structural properties of amyloid-like fibrils formed from / β plus-plus">2-microglobulin by limited proteolysis and mass spectrometry. / Rapid Commun. Mass Spectrom. plus-plus">2006, / 20, 1628-636. p://dx.doi.org/10.1002/rcm.2482">CrossRef
35. Smith, A. M.; Jahn, T. J.; Ashcroft, A. E.; Radford, S. E. Direct observation of oligomeric species formed in the early stages of amyloid fibril formation using electrospray ionization mass spectrometry. / J. Mol. Biol. plus-plus">2006, / 364, 9-9. p://dx.doi.org/10.1016/j.jmb.2006.08.081">CrossRef
36. Borysik, A. J. H.; Read, P.; Little, D. R.; Bateman, R. H.; Radford, S. E.; Ashcroft, A. E. Separation of / β plus-plus">2-microglobulin conformers by high-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to electrospray mass spectrometry. / Rapid Commun. Mass Spectrom. plus-plus">2004, / 18, 2229-234. p://dx.doi.org/10.1002/rcm.1613">CrossRef
37. Margoliash, E.; Smith, E. L.; Kreil, G.; Tuppy, H. Amino-acid sequence of horse heart cytochrome / c: The complete amino-acid sequence. / Nature plus-plus">1961, / 192, 1125-127. p://dx.doi.org/10.1038/1921125a0">CrossRef
38. Badman, E. R.; Myung, S.; Clemmer, D. E. Evidence for unfolding and refolding of gas-phase cytochrome / c ions in a Paul trap. / J. Am. Soc. Mass Spectrom. plus-plus">2005, / 16, 1493-497. p://dx.doi.org/10.1016/j.jasms.2005.04.013">CrossRef
39. Clemmer, D. E.; Hudgins, R. R.; Jarrold, M. F. Naked protein conformation: Cytochrome / c in the gas phase. / J. Am. Chem. Soc. plus-plus">1995, / 117, 10141-0142. p://dx.doi.org/10.1021/ja00145a037">CrossRef
40. Valentine, S. J.; Clemmer, D. E. H/D exchange levels of shape-resolved cytochrome / c conformers in the gas phase. / J. Am. Chem. Soc. plus-plus">1997, / 119, 3558-566. p://dx.doi.org/10.1021/ja9626751">CrossRef
41. Guevremont, R.; Siu, K. W. M.; Wang, J.; Ding, L. Combined ion mobility/time-of-flight mass spectrometry study of electrospray-generated ions. / Anal. Chem. plus-plus">1997, / 69, 3959-965. p://dx.doi.org/10.1021/ac970359e">CrossRef
42. Covey, T.; Douglas, D. J. Collision cross sections for protein ions. / J. Am. Soc. Mass Spectrom. plus-plus">1993, / 4, 616-23. p://dx.doi.org/10.1016/1044-0305(93)85025-S">CrossRef
43. Pamer, E.; Cresswell, P. Mechanisms of MHC class I-restricted antigen processing. / Annu. Rev. Immunol. plus-plus">1998, / 16, 323-58. p://dx.doi.org/10.1146/annurev.immunol.16.1.323">CrossRef
44. Floege, J.; Bartsch, A.; Schulze, M.; Shaldon, S.; Koch, K. M.; Smeby, L. C. Clearance and synthesis rates of / β plus-plus">2-microglobulin in hemodialyzed patients and normals. / J. Lab. Clin. Med. plus-plus">1991, / 118, 153-65.
45. Floege, J.; Ketteler, M. / β plus-plus">2-Microglobulin-derived amyloidosis: An update. / Kidney Int. plus-plus">2001, / 59, 164-71. p://dx.doi.org/10.1046/j.1523-1755.2001.07823.x">CrossRef
46. Uversky, V. N.; Fink, A. L. Conformational constraints for amyloid fibrillation: The importance of being unfolded. / Biochim. Biophys. Acta. plus-plus">2004, / 1698, 131-53.
47. Platt, G. W.; McParland, V. J.; Kalverda, A. P.; Homans, S. W.; Radford, S. E. Dynamics in the unfolded state of / β plus-plus">2-microglobulin studied by NMR. / J. Mol. Biol. plus-plus">2005, / 346, 279-94. p://dx.doi.org/10.1016/j.jmb.2004.11.035">CrossRef
48. Trinh, C. H.; Smith, D. P.; Kalverda, A. P.; Phillips, S. E.; Radford, S. E. Crystal structure of monomeric human / β plus-plus">2-microglobulin reveals clues to its amyloidogenic properties. / Proc. Natl. Acad. Sci. U.S.A. plus-plus">2002, / 99, 9771-776. p://dx.doi.org/10.1073/pnas.152337399">CrossRef
49. Myers, S. L.; Jones, S.; Jahn, T. J.; Morten, I. J.; Tennent, G. A.; Hewitt, E. W.; Radford, S. E. A systematic study of the effect of physiological factors on / β plus-plus">2-microglobulin amyloid formation at neutral pH. / Biochemistry plus-plus">2006, / 45, 2311-321. p://dx.doi.org/10.1021/bi052434i">CrossRef
50. Gosal, W. S.; Morten, I. J.; Hewitt, E. W.; Smith, D. A.; Thomson, N. H.; Radford, S. E. Competing pathways determine fibril morphology in the self-assembly of / β plus-plus">2-microglobulin into amyloid. / J. Mol. Biol. plus-plus">2005, / 351, 850-64. p://dx.doi.org/10.1016/j.jmb.2005.06.040">CrossRef
51. Jahn, T. J.; Parker, M. J.; Homans, S. W.; Radford, S. E. Amyloid formation under physiological conditions proceeds via a native-like folding intermediate. / Nat. Struct. Mol. Biol. plus-plus">2006, / 13, 195-01. p://dx.doi.org/10.1038/nsmb1058">CrossRef - 作者单位：David P. Smith (1)
Kevin Giles (2)
Robert H. Bateman (2)
Sheena E. Radford (1)
Alison E. Ashcroft (1)
1. Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Astbury Building, LS2 9JT, Leeds, UK
2. Waters MS Technologies Centre, Micromass UK Ltd., Manchester, United Kingdom
文摘
The precise mechanism of protein folding remains elusive and there is a deficiency of biophysical techniques that are capable of monitoring the individual behavior of copopulated protein conformers during the folding process. Herein, an ion mobility spectrometry (IMS) device integrated with electrospray ionization mass spectrometry (ESI-MS) has been used to successfully separate and analyze protein conformers differing in cross section and/or charge state. In an initial test, an ensemble of folded and partially folded conformers of the protein cytochrome c was separated. A detailed study undertaken on the amyloidogenic protein β 2-microglobulin (β 2m), which forms fibrils by protein unfolding followed by self-aggregation and is responsible for the disease dialysis-related amyloidosis, has generated important insights into its folding landscape. Initially, a systematic titration of β 2m over the pH range 2 to 7 using ESI-IMS-MS allowed individual conformers to be monitored and quantified throughout the acid denaturation process. Furthermore, a comparison of wild-type β 2m with single and double amino acid variants with a range of folding stabilities and propensities for amyloid fibril formation has provided illuminating evidence of the role of different conformers in protein stability and amyloidogenic aggregation. The ESI-IMS-MS data presented here not only demonstrate an important and informative further dimension to ESI-MS, but also illustrate the potential of the ESI-IMS-MS technique for unravelling protein folding enigmas in general and studying protein misfolding diseases in particular.