Conformations and assembly of amyloid oligomers by electrospray ionisation - ion mobility spectrometry - mass spectrometry

Current Analytical Chemistry

Volumn 9, Issue 2, 2013, Pages 165-180

  Illes Toth, Eva ^a   Smith, David P ^a  

^a SHEFFIELD HALLAM UNIVERSITY   (United Kingdom)

Author keywords

Amyloid; Ion mobility spectrometry; Mass spectrometry; Oligomer; Protein folding; Protein misfolding

Indexed keywords

CONFORMATIONS; ELECTROSPRAY IONIZATION; GLYCOPROTEINS; ION MOBILITY SPECTROMETERS; IONS; MASS SPECTROMETRY; PROTEINS; SELF ASSEMBLY;

AMYLOID; AMYLOID DISEASE; AMYLOID STRUCTURES; CONFORMATIONAL CHANGE; DISEASE STATE; FOLDED PROTEINS; ION MOBILITY SPECTROMETRY; PROTEIN CONFORMATION CHANGES; PROTEIN FOLDINGS; PROTEIN MISFOLDING;

OLIGOMERS;

EID: 84875308216     PISSN: 15734110     EISSN: None     Source Type: Journal    
DOI: 10.2174/157341113805218992     Document Type: Article

References (110)

1. Sipe, J. D.; Benson, M. D.; Buxbaum, J. N.; Ikeda, S.; Merlini, G.; Saraiva, M. J.; Westermark, P. Amyloid fibril protein nomenclature: 2010 recommendations from the nomenclature committee of the International Society of Amyloidosis Amyloid 2010, 17, 101-104.
2. Westermark, P.; Benson, M. D.; Buxbaum, J. N.; Cohen, A. S.; Frangione, B.; Ikeda, S.; Masters, C. L.; Merlini, G.; Saraiva, M. J.; Sipe, J. D. A primer of amyloid nomenclature Amyloid 2007, 14, 179-183.
3. Sunde, M.; Blake, C. The structure of amyloid fibrils by electron microscopy and X-ray diffraction. Advances in Protein Chemistry 1997, 50, 123-159.
4. Pedersen, J. S.; Andersen, C. B.; Otzen, D. E. Amyloid structure one but not the same: the many levels of fibrillar polymorphism FEBS J. 2010, 277, 4591-4601.
5. Mondragon-Rodriguez, S.; Basurto-Islas, G.; Lee, H. G.; Perry, G.; Zhu, X.; Castellani, R. J.; Smith, M. A. Causes versus effects: the increasing complexities of Alzheimer's disease pathogenesis Expert Rev. Neurother 2010, 10, 683-691.
6. Heegaard, N. H. Beta(2)-Microglobulin: from Physiology to Amy-loidosis. Amyloid 2009, 16, 151-173.
7. Rapezzi, C.; Quarta, C. C.; Riva, L.; Longhi, S.; Gallelli, I.; Lorenzini, M.; Ciliberti, P.; Biagini, E.; Salvi, F.; Branzi, A. Transthyretin-related amyloidoses and the heart: a clinical overview Nat. Rev. Cardiol. 2010, 7, 398-408.
8. Norrby, E. Prions and protein-folding diseases J. Intern. Med. 2011, 270, 1-14.
9. Chiti, F.; Dobson, C. M. Protein misfolding, functional amyloid, and human disease Annu. Rev. Biochem. 2006, 75, 333-366.
10. Eichner, T.; Radford, S. E. A diversity of assembly mechanisms of a generic amyloid fold Mol. Cell 2011, 43, 8-18.
11. Zerovnik, E.; Stoka, V.; Mirtic, A.; Guncar, G.; Grdadolnik, J.; Staniforth, R. A.; Turk, D.; Turk, V. Mechanisms of amyloid fibril formation-focus on domain-swapping FEBS J. 2011, 278, 2263-2282.
12. Lashuel, H. A.; Lansbury, P. T. Jr Are amyloid diseases caused by protein aggregates that mimic bacterial pore-forming toxins? Q. Rev. Biophys. 2006, 39, 167-201.
13. Kayed, R.; Glabe, C. G. Conformation-dependent anti-amyloid oligomer antibodies. Methods Enzymol. 2006, 413, 326-344.
14. Lesne, S.; Koh, M. T.; Kotilinek, L.; Kayed, R.; Glabe, C. G.; Yang, A.; Gallagher, M.; Ashe, K. H. A specific amyloid-beta protein assembly in the brain impairs memory Nature 2006, 440, 352-357.
15. Winner, B.; Jappelli, R.; Maji, S. K.; Desplats, P. A.; Boyer, L.; Aigner, S.; Hetzer, C; Loher, T.; Vilar, M.; Campioni, S.; Tzitz-ilonis, C; Soragni, A.; Jessberger, S.; Mira, H.; Consiglio, A.; Pham, E.; Masliah, E.; Gage, F. H.; Riek, R. In vivo demonstration that alpha-synuclein oligomers are toxic Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 4194-4199.
16. Glabe, C. G. Structural classification of toxic amyloid oligomers J. Biol. Chem. 2008, 283, 29639-29643.
17. Xue, W. F.; Hellewell, A. L.; Gosal, W. S.; Homans, S. W.; Hewitt, E. W.; Radford, S. E. Fibril fragmentation enhances amyloid cytotoxicity J. Biol. Chem. 2009, 284, 34272-34282.
18. Ilag, L. L.; Videler, H.; McKay, A. R.; Sobott, F.; Fucini, P.; Nier-haus, K. H.; Robinson, C. V. Heptameric (L12)6/L10 rather than canonical pentameric complexes are found by tandem MS of intact ribosomes from thermophilic bacteria. Proc. Natl. Acad. Sci. U. S. A. 2005, 102, 8192-7.
19. Rostom, A. A.; Robinson, C. V. Detection of the Intact GroEL Chaperonin Assembly by Mass Spectrometry. J. Am. Chem. Soc. 1999, 121, 4718-4719.
20. Tito, M. A.; Tars, K.; Valegard, K.; Hajdu, J.; Robinson, C. V. Electrospray Time-of-Flight Mass Spectrometry of the Intact MS2 Virus Capsid. J. Am. Chem. Soc. 2000, 122, 3550-3551.
21. Smith, A. M.; Jahn, T. R.; Ashcroft, A. E.; Radford, S. E. Direct observation of oligomeric species formed in the early stages of amyloid fibril formation using electrospray ionisation mass spectrometry. J. Mo.l Biol. 2006, 364, 9-19.
22. Nettleton, E. J.; Tito, P.; Sunde, M.; Bouchard, M.; Dobson, C. M.; Robinson, C. V. Characterization of the oligomeric states of insulin in self-assembly and amyloid fibril formation by mass spectrometry. Biophys. J. 2000, 79, 1053-65.
23. Larson, J. L.; Ko, E.; Miranker, A. D. Direct measurement of islet amyloid polypeptide fibrillogenesis by mass spectrometry. Protein Sci. 2000, 9, 427-31.
24. Baskakov, I. V.; Legname, G.; Baldwin, M. A.; Prusiner, S. B.; Cohen, F. E. Pathway complexity of prion protein assembly into amyloid. J. Biol. Chem. 2002, 277, 21140-8.
25. Jablonowska, A.; Bakun, M.; Kupniewska-Kozak, A.; Dadlez, M. Alzheimer's disease Abeta peptide fragment 10-30 forms a spectrum of metastable oligomers with marked preference for N to N and C to C monomer termini proximity. J. Mol. Biol. 2004, 344, 1037-49.
26. Bernstein, S. L.; Dupuis, N. F.; Laz, N. D.; Wyttenbach, T.; Con-dron, M. M.; Bitan, G.; Teplow, B. D.; Shea, J.; Ruotolo, B. T.; Robinson, C. V.; Bowers, M. T. Amyloid-P protein oligomeriza-tion and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease. Nat. Chem. 2009, 1, 326-331; 326.
27. Uetrecht, C; Rose, R. J.; van Duijn, E.; Lorenzen, K.; Heck, A. J. Ion mobility mass spectrometry of proteins and protein assemblies. Chem. Soc. Rev. 2010, 39, 1633-1655.
28. Kanu, A. B.; Dwivedi, P.; Tam, M.; Matz, L.; Hill, H. H., Jr Ion mobility-mass spectrometry J. Mass Spectrom. 2008, 43, 1-22.
29. Pringle, S.; Giles, K.; Wildergoose, J.; Williams, J.; Sldae, S.; Thalassinos, K.; Bateman, R.; Bowers, M.; Scrivens, J. An investigation of the mobility separation of some peptide and protein ions using a new hybrid quadrupole/travelling wave IMS/oa-ToF in- strument International Journal of Mass Spectrometry 2007, 261, 1-12.
30. Scarff, C. A.; Thalassinos, K.; Hilton, G. R.; Scrivens, J. H. Travelling wave ion mobility mass spectrometry studies of protein structure: biological significance and comparison with X-ray crystallography and nuclear magnetic resonance spectroscopy measurements Rapid Commun. Mass Spectrom. 2008, 22, 3297-3304.
31. Smith, D. P.; Knapman, T. W.; Malham, R. W.; Berryman, J. T.; Radford, S. E.; Ashcroft, A. E. Deciphering drift time measurements from travelling wave ion mobility spectrometry - mass spectrometry studies. EJMS 2009, 15, 113-130.
32. Bush, M. F.; Hall, Z.; Giles, K.; Hoyes, J.; Robinson, C. V.; Ruo-tolo, B. T. Collision cross sections of proteins and their complexes: a calibration framework and database for gas-phase structural biology Anal. Chem. 2010, 82, 9557-9565.
33. Ruotolo, B. T.; Benesch, J. L.; Sandercock, A. M.; Hyung, S. J.; Robinson, C. V. Ion mobility-mass spectrometry analysis of large protein complexes. Nat. Protoc. 2008, 3, 1139-52.
34. Jurneczko, E.; Barran, P. E. How useful is ion mobility mass spectrometry for structural biology? The relationship between protein crystal structures and their collision cross sections in the gas phase Analyst 2011, 136, 20-28.
35. Politis, A.; Park, A. Y.; Hyung, S. J.; Barsky, D.; Ruotolo, B. T.; Robinson, C. V. Integrating ion mobility mass spectrometry with molecular modelling to determine the architecture of multiprotein complexes PLoS One 2010, 5, e12080.
36. Ruotolo, B. T.; 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 2005, 310, 1658-1661.
37. Smith, D. P.; Radford, S. E.; Ashcroft, A. E. Elongated oligomers in p2-microglobulin amyloid assembly revealed by ion mobility spectrometry-mass spectrometry. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 6794-6798.
38. Mesleh, M. F.; Hunter, J. M.; Shvartsburg, A. A.; Schatz, G. C; Jarrold, M. F. Structural Information from Ion Mobility Measurements: Effects of the Long-Range Potential J. Phys. Chem. 1996, 100, 16082-16086.
39. Williams, J. P.; Lough, J. A.; Campuzano, I.; Richardson, K.; Sadler, P. J. Use of ion mobility mass spectrometry and a collision cross-section algorithm to study an organometallic ruthenium anticancer complex and its adducts with a DNA oligonucleotide Rapid Commun. Mass Spectrom. 2009, 23, 3563-3569.
40. Beardsley, R. L.; Jones, C. M.; Galhena, A. S.; Wysocki, V. H. Noncovalent protein tetramers and pentamers with n charges yield monomers with n/4 and n/5 charges Anal. Chem. 2009, 81, 1347-1356.
41. Uetrecht, C; Versluis, C; Watts, N. R.; Wingfield, P. T.; Steven, A. C; Heck, A. J. Stability and shape of hepatitis B virus capsids in vacuo. Angew. Chem. Int. Ed Engl. 2008, 47, 6247-6251.
42. Klein, W. L.; Stine, W. B., Jr; Teplow, D. B. Small assemblies of unmodified amyloid beta-protein are the proximate neurotoxin in Alzheimer's disease Neurobiol. Aging 2004, 25, 569-580.
43. Lesne, S.; Koh, M. T.; Kotilinek, L.; Kayed, R.; Glabe, C. G.; Yang, A.; Gallagher, M.; Ashe, K. H. A specific amyloid-beta protein assembly in the brain impairs memory. Nature 2006, 440, 352-7.
44. Bitan, G.; Teplow, D. B. Rapid photochemical cross-linking--a new tool for studies of metastable, amyloidogenic protein assemblies. Acc. Chem. Res. 2004, 37, 357-64.
45. Duce, J. A.; Bush, A. I. Biological metals and Alzheimer's disease: implications for therapeutics and diagnostics Prog. Neurobiol. 2010, 92, 1-18.
46. Ferreira, S. T.; Klein, W. L. The Abeta oligomer hypothesis for synapse failure and memory loss in Alzheimer's disease Neurobiol. Learn. Mem. 2011.
47. Baumketner, A.; Bernstein, S. L.; Wyttenbach, T.; Bitan, G.; Teplow, D. B.; Bowers, M. T.; Shea, J. E. Amyloid beta-protein monomer structure: a computational and experimental study Protein Sci. 2006, 15, 420-428.
48. Ionut Iurascu, M.; Cozma, C; Tomczyk, N.; Rontree, J.; Desor, M.; Drescher, M.; Przybylski, M. Structural characterization of beta-amyloid oligomer-aggregates by ion mobility mass spectrometry and electron spin resonance spectroscopy Anal. Bioanal Chem. 2009, 395, 2509-2519.
49. Jan, A.; Gokce, O.; Luthi-Carter, R.; Lashuel, H. A. The ratio of monomeric to aggregated forms of Abeta40 and Abeta42 is an important determinant of amyloid-beta aggregation, fibrillogenesis, and toxicity J. Biol. Chem. 2008, 283, 28176-28189.
50. Murray, M. M.; Bernstein, S. L.; Nyugen, V.; Condron, M. M.; Teplow, D. B.; Bowers, M. T. Amyloid beta protein: Abeta40 inhibits Abeta42 oligomerization J. Am. Chem. Soc. 2009, 131, 6316-6317.
51. Bernstein, S. L.; Wyttenbach, T.; Baumketner, A.; Shea, J. E.; Bitan, G.; Teplow, D. B.; Bowers, M. T. Amyloid beta-protein: monomer structure and early aggregation states of Abeta42 and its Pro19 alloform J. Am. Chem. Soc. 2005, 127, 2075-2084.
52. Kloniecki, M.; Jablonowska, A.; Poznanski, J.; Langridge, J.; Hughes, C.; Campuzano, I.; Giles, K.; Dadlez, M. Ion mobility separation coupled with MS detects two structural states of Alzheimer's disease Abeta1-40 peptide oligomers J. Mol. Biol. 2011, 407, 110-124.
53. Smith, D. P.; Woods, L. A.; Radford, S. E.; Ashcroft, A. E. Structure and Dynamics of Oligomeric Intermediates in beta(2)-Microglobulin Self-Assembly Biophys. J. 2011, 101, 1238-1247.
54. Welzel, A. T.; Walsh, D. M. Aberrant protein structure and diseases of the brain Ir. J. Med. Sci. 2011, 180, 15-22.
55. Uversky, V. N. Alpha-synuclein misfolding and neurodegenerative diseases Curr. Protein Pept. Sci. 2008, 9, 507-540.
56. Orcellet, M. L.; Fernandez, C. O. Structures behind the amyloid aggregation of alpha-synuclein: an NMR based approach Curr. Protein Pept. Sci. 2011, 12, 188-204.
57. Uversky, V. N.; Eliezer, D. Biophysics of Parkinson's disease: structure and aggregation of alpha-synuclein Curr. Protein Pept. Sci. 2009, 10, 483-499.
58. Brown, D. R. Oligomeric alpha-synuclein and its role in neuronal death IUBMB Life 2010, 62, 334-339.
59. Uversky, V. N.; Eliezer, D. Biophysics of Parkinson's disease: structure and aggregation of alpha-synuclein. Curr. Protein Pept. Sci. 2009, 10, 483-499.
60. Uversky, V. N. Alpha-synuclein misfolding and neurodegenerative diseases. Curr Protein Pept Sci 2008, 9, 507-40.
61. Uversky, V. N.; Lee, H. J.; Li, J.; Fink, A. L.; Lee, S. J. Stabilization of partially folded conformation during alpha-synuclein oli-gomerization in both purified and cytosolic preparations. J. Biol. Chem. 2001, 276, 43495-8.
62. van Rooijen, B. D.; Claessens, M. M.; Subramaniam, V. Membrane interactions of oligomeric alpha-synuclein: potential role in Parkinson's disease Curr. Protein Pept. Sci. 2010, 11, 334-342.
63. Bernstein, S. L.; Liu, D.; Wyttenbach, T.; Bowers, M. T.; Lee, J. C.; Gray, H. B.; Winkler, J. R. Alpha-synuclein: stable compact and extended monomeric structures and pH dependence of dimer formation. J. Am. Soc. Mass Spectrom. 2004, 15, 1435-43.
64. Antony, T.; Hoyer, W.; Cherny, D.; Heim, G.; Jovin, T. M.; Subramaniam, V. Cellular polyamines promote the aggregation of alpha-synuclein J. Biol. Chem. 2003, 278, 3235-3240.
65. Fernandez, C. O.; Hoyer, W.; Zweckstetter, M.; Jares-Erijman, E. A.; Subramaniam, V.; Griesinger, C.; Jovin, T. M. NMR of alpha-synuclein-polyamine complexes elucidates the mechanism and kinetics of induced aggregation EMBO J. 2004, 23, 2039-2046.
66. Grabenauer, M.; Bernstein, S. L.; Lee, J. C.; Wyttenbach, T.; Du-puis, N. F.; Gray, H. B.; Winkler, J. R.; Bowers, M. T. Spermine binding to Parkinson's protein alpha-synuclein and its disease-related A30P and A53T mutants J. Phys. Chem. B 2008, 112, 11147-11154.
67. Binolfi, A.; Rasia, R. M.; Bertoncini, C. W.; Ceolin, M.; Zweck-stetter, M.; Griesinger, C.; Jovin, T. M.; Fernandez, C. O. Interaction of alpha-synuclein with divalent metal ions reveals key differences: a link between structure, binding specificity and fibrillation enhancement. J. Am. Chem. Soc. 2006, 128, 9893-901.
68. Lee, J. C.; Gray, H. B.; Winkler, J. R. Copper(II) binding to alpha-synuclein, the Parkinson's protein J. Am. Chem. Soc. 2008, 130, 6898-6899.
69. Hong, L.; Simon, J. D. Insights into the thermodynamics of copper association with amyloid-beta, alpha-synuclein and prion proteins Metallomics 2011, 3, 262-266.
70. Dobo, A.; Kaltashov, I. A. Detection of multiple protein conforma-tional ensembles in solution via deconvolution of charge-state distributions in ESI MS Anal. Chem. 2001, 73, 4763-4773.
71. Munishkina, L. A.; Phelan, C.; Uversky, V. N.; Fink, A. L. Con-formational behavior and aggregation of alpha-synuclein in organic solvents: modeling the effects of membranes Biochemistry 2003, 42, 2720-2730.
72. Frimpong, A. K.; Abzalimov, R. R.; Uversky, V. N.; Kaltashov, I. A. Characterization of intrinsically disordered proteins with elec-trospray ionization mass spectrometry: conformational heterogeneity of alpha-synuclein. Proteins 2010, 78, 714-722.
73. Natalello, A.; Benetti, F.; Doglia, S. M.; Legname, G.; Grandori, R. Compact conformations of alpha-synuclein induced by alcohols and copper Proteins 2011, 79, 611-621.
74. Bartels, T.; Choi, J. G.; Selkoe, D. J. a-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation Nature 2011.
75. Prusiner, S. B. Novel proteinaceous infectious particles cause scra-pie Science 1982, 216, 136-144.
76. Prigent, S.; Rezaei, H. PrP assemblies: spotting the responsible regions in prion propagation Prion 2011, 5, 69-75.
77. Jang, S.; Shin, S. Amyloid beta-peptide oligomerization in silico: dimer and trimer J Phys Chem B 2006, 110, 1955-1958.
78. Grabenauer, M.; Wu, C.; Soto, P.; Shea, J. E.; Bowers, M. T. Oli-gomers of the prion protein fragment 106-126 are likely assembled from beta-hairpins in solution, and methionine oxidation inhibits assembly without altering the peptide's monomeric conformation. J. Am. Chem. Soc. 2010, 132, 532-539.
79. Hilton, G. R.; Thalassinos, K.; Grabenauer, M.; Sanghera, N.; Slade, S. E.; Wyttenbach, T.; Robinson, P. J.; Pinheiro, T. J.; Bowers, M. T.; Scrivens, J. H. Structural analysis of prion proteins by means of drift cell and traveling wave ion mobility mass spec-trometry. J. Am. Soc. Mass Spectrom. 2010, 21, 845-854.
80. Grabenauer, M.; Wyttenbach, T.; Sanghera, N.; Slade, S. E.; Pin-heiro, T. J.; Scrivens, J. H.; Bowers, M. T. Conformational stability of Syrian hamster prion protein PrP(90-231) J. Am. Chem. Soc. 2010, 132, 8816-8818.
81. Yamamoto, S.; Kazama, J. J.; Narita, I.; Naiki, H.; Gejyo, F. Recent progress in understanding dialysis-related amyloidosis Bone 2009, 45 Suppl 1, S39-S42.
82. 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 beta 2-microglobulin into Amyloid. J. Mol. Biol. 2005, 351, 850-864.
83. Kad, N. M.; Myers, S. L.; Smith, D. P.; Smith, D. A.; Radford, S. E.; Thomson, N. H. Hierarchical assembly of beta 2-microglobulin amyloid in vitro revealed by atomic force microscopy. J. Mol. Biol. 2003, 330, 785-797.
84. Platt, G. W.; Radford, S. E. Glimpses of the molecular mechanisms of beta2-microglobulin fibril formation in vitro: aggregation on a complex energy landscape FEBS Lett. 2009, 583, 2623-2629.
85. Xue, W. F.; Homans, S. W.; Radford, S. E. Systematic analysis of nucleation-dependent polymerization reveals new insights into the mechanism of amyloid self-assembly. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 8926-8931.
86. Smith, D. P.; Giles, K.; Bateman, R. H.; Radford, S. E.; Ashcroft, A. E. Monitoring copopulated conformational states during protein folding events using electrospray ionization-ion mobility spec-trometry-mass spectrometry. J. Am. Soc. Mass Spectrom. 2007, 18, 2180-2190.
87. Santambrogio, C.; Ricagno, S.; Sobott, F.; Colombo, M.; Bo-lognesi, M.; Grandori, R. Characterization of beta2-microglobulin conformational intermediates associated to different fibrillation conditions J. Mass Spectrom. 2011, 46, 734-741.
88. Xue, W. F.; Homans, S. W.; Radford, S. E. Systematic analysis of nucleation-dependent polymerization reveals new insights into the mechanism of amyloid self-assembly. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 8926-31.
89. Woods, L. A.; Platt, G. W.; Hellewell, A. L.; Hewitt, E. W.; Ho-mans, S. W.; Ashcroft, A. E.; Radford, S. E. Ligand binding to distinct states diverts aggregation of an amyloid-forming protein Nat. Chem. Biol. 2011, 7, 730-739.
90. Westermark, P.; Andersson, A.; Westermark, G. T. Islet amyloid polypeptide, islet amyloid, and diabetes mellitus Physiol. Rev. 2011, 91, 795-826.
91. Kayed, R.; Sokolov, Y.; Edmonds, B.; McIntire, T. M.; Milton, S. C.; Hall, J. E.; Glabe, C. G. Permeabilization of lipid bilayers is a common conformation-dependent activity of soluble amyloid oligomers in protein misfolding diseases. J. Bio.l Chem. 2004, 279, 46363-6.
92. Luca, S.; Yau, W. M.; Leapman, R.; Tycko, R. Peptide conformation and supramolecular organization in amylin fibrils: constraints from solid-state NMR Biochemistry 2007, 46, 13505-13522.
93. Porat, Y.; Kolusheva, S.; Jelinek, R.; Gazit, E. The human islet amyloid polypeptide forms transient membrane-active prefibrillar assemblies Biochemistry 2003, 42, 10971-10977.
94. Ahmad, E.; Ahmad, A.; Singh, S.; Arshad, M.; Khan, A. H.; Khan, R. H. A mechanistic approach for islet amyloid polypeptide aggregation to develop anti-amyloidogenic agents for type-2 diabetes Biochimie 2011, 93, 793-805.
95. Williamson, J. A.; Miranker, A. D. Direct detection of transient alpha-helical states in islet amyloid polypeptide Protein Sci. 2007, 16, 110-117.
96. Wei, L.; Jiang, P.; Yau, Y. H.; Summer, H.; Shochat, S. G.; Mu, Y.; Pervushin, K. Residual structure in islet amyloid polypeptide mediates its interactions with soluble insulin Biochemistry 2009, 48, 2368-2376.
97. Kayed, R.; Bernhagen, J.; Greenfield, N.; Sweimeh, K.; Brunner, H.; Voelter, W.; Kapurniotu, A. Conformational transitions of islet amyloid polypeptide (IAPP) in amyloid formation in vitro J. Mol. Biol. 1999, 287, 781-796.
98. Dupuis, N. F.; Wu, C.; Shea, J. E.; Bowers, M. T. Human islet amyloid polypeptide monomers form ordered beta-hairpins: a possible direct amyloidogenic precursor J. Am. Chem. Soc. 2009, 131, 18283-18292.
99. Dupuis, N. F.; Wu, C.; Shea, J. E.; Bowers, M. T. The amyloid formation mechanism in human IAPP: dimers have beta-strand monomer-monomer interfaces J. Am. Chem. Soc. 2011, 133, 7240-7243.
100. Bleiholder, C.; Dupuis, N. F.; Wyttenbach, T.; Bowers, M. T. Ion mobility-mass spectrometry reveals a conformational conversion from random assembly to beta-sheet in amyloid fibril formation Nat. Chem. 2011, 3, 172-177.
101. Nelson, R.; Eisenberg, D. Recent atomic models of amyloid fibril structure Curr. Opin. Struct. Biol. 2006, 16, 260-265.
102. Nelson, R.; Sawaya, M. R.; Balbirnie, M.; Madsen, A. O.; Riekel, C.; Grothe, R.; Eisenberg, D. Structure of the cross-beta spine of amyloid-like fibrils Nature 2005, 435, 773-778.
103. Sawaya, M. R.; Sambashivan, S.; Nelson, R.; Ivanova, M. I.; Siev-ers, S. A.; Apostol, M. I.; Thompson, M. J.; Balbirnie, M.; Wiltzius, J. J.; McFarlane, H. T.; Madsen, A. O.; Riekel, C.; Eisen-berg, D. Atomic structures of amyloid cross-beta spines reveal varied steric zippers Nature 2007, 447, 453-457.
104. Quintas, A., Vaz, D.C., Cardoso, I., Saraiva, M.J., Brito, R.M. Tetramer dissociation and monomer partial unfolding precedes pro-tofibril formation in amyloidogenic transthyretin variants. J. Bio. Chem. 2001, 276,27207-27213.
105. Ruotolo, B. T.; Hyung, S. J.; Robinson, P. M.; Giles, K.; Bateman, R. H.; Robinson, C. V. Ion mobility-mass spectrometry reveals long-lived, unfolded intermediates in the dissociation of protein complexes. Angew Chem Int Ed Engl 2007, 46, 8001-4.
106. Keetch, C. A.; Bromley, E. H.; McCammon, M. G.; Wang, N.; Christodoulou, J.; Robinson, C. V. L55P transthyretin accelerates subunit exchange and leads to rapid formation of hybrid tetramers J. Biol. Chem. 2005, 280, 41667-41674.
107. Hyung, S. J.; Robinson, C. V.; Ruotolo, B. T. Gas-phase unfolding and disassembly reveals stability differences in ligand-bound mul-tiprotein complexes Chem. Biol. 2009, 16, 382-390.
108. Pagel, K.; Hyung, S. J.; Ruotolo, B. T.; Robinson, C. V. Alternate dissociation pathways identified in charge-reduced protein complex ions Anal. Chem. 2010, 82, 5363-5372.
109. Hyung, S. J.; Deroo, S.; Robinson, C. V. Retinol and retinol-binding protein stabilize transthyretin via formation of retinol transport complex ACS Chem. Biol. 2010, 5, 1137-1146.
110. Kolstoe, S. E.; Mangione, P. P.; Bellotti, V.; Taylor, G. W.; Ten-nent, G. A.; Deroo, S.; Morrison, A. J.; Cobb, A. J.; Coyne, A.; McCammon, M. G.; Warner, T. D.; Mitchell, J.; Gill, R.; Smith, M. D.; Ley, S. V.; Robinson, C. V.; Wood, S. P.; Pepys, M. B. Trapping of palindromic ligands within native transthyretin prevents amyloid formation Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 20483-20488.