Structures behind the amyloid aggregation of α-synuclein: An NMR based approach

Current Protein and Peptide Science

Volumn 12, Issue 3, 2011, Pages 188-205

  Orcellet, María L ^a   Fernández, Claudio O ^a,b  

^a UNIVERSIDAD NACIONAL DE ROSARIO   (Argentina)

^b MAX PLANCK INSTITUTE FOR BIOPHYSICAL CHEMISTRY   (Germany)

Author keywords

Amyloid; Intrinsically disordered proteins; NMR spectroscopy; Parkinson's disease; Structural biology

Indexed keywords

ALPHA SYNUCLEIN; AMYLIN; AMYLOID; AMYLOID BETA PROTEIN; BETA 2 MICROGLOBULIN; BETA SYNUCLEIN; COPPER ZINC SUPEROXIDE DISMUTASE; GAMMA SYNUCLEIN; HUNTINGTIN; IMMUNOGLOBULIN LIGHT CHAIN; OLIGOMER; PREALBUMIN; PRION PROTEIN; SNARE PROTEIN;

ALPHA HELIX; ALZHEIMER DISEASE; AMINO ACID SEQUENCE; AMINO TERMINAL SEQUENCE; AMYLOIDOSIS; CARBOXY TERMINAL SEQUENCE; CATARACT; CONCENTRATION (PARAMETERS); CREUTZFELDT JAKOB DISEASE; DIFFUSE LEWY BODY DISEASE; ELECTRON MICROSCOPY; FAMILIAL AMYLOIDOSIS; HUMAN; HUNTINGTON CHOREA; HYDRODYNAMICS; HYDROGEN BOND; HYDROPHOBICITY; IMMUNOHISTOCHEMISTRY; MOLECULAR DYNAMICS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PARKINSON DISEASE; PATHOGENESIS; PROTEIN AGGREGATION; PROTEIN ASSEMBLY; PROTEIN CONFORMATION; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN MODIFICATION; PROTEIN SECONDARY STRUCTURE; PROTEIN STRUCTURE; PROTEIN TARGETING; REVIEW; SHY DRAGER SYNDROME; STRUCTURE ANALYSIS; SYNAPSE VESICLE; X RAY DIFFRACTION;

ALPHA-SYNUCLEIN; AMINO ACID SEQUENCE; AMYLOID; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; MOLECULAR SEQUENCE DATA; PARKINSON DISEASE; PROTEIN FOLDING; PROTEOSTASIS DEFICIENCIES; SEQUENCE ALIGNMENT;

EID: 79959325087     PISSN: 13892037     EISSN: 18755550     Source Type: Journal    
DOI: 10.2174/138920311795860160     Document Type: Review

References (150)

1. Chiti, F.; Dobson, C.M. Protein misfolding, functional amyloid and human disease. Annu. Rev. Biochem., 2006, 75, 333-366.
2. Forno, L.S. Neuropathology of Parkinson's disease. J. Neuropathol. Exp. Neurol., 1996, 55, 259-272.
3. Lewy, F.H. In Handbuch der Neurologie; Lewandowsky, M., Abelsdorff, G., Ed.; Springer-Verlag: Berlin, 1912; Vol. 3, 920-933.
4. 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 alpha-synuclein gene identified in families with Parkinson's disease. Science, 1997, 276, 2045-2047.
5. Spillantini, M.G.; Schmidt, M.L.; Lee, V.M.; Trojanowski, J.Q.; Jakes, R.; Goedert, M. Alpha-synuclein in Lewy bodies. Nature, 1997, 388, 839-840.
6. Goedert, M. Alpha-synuclein and neurodegenerative diseases. Nat. Rev. Neurosci., 2001, 2, 492-501.
7. Kruger, R.; Kuhn, W.; Muller, T.; Woitalla, D.; Graeber, M.; Kosel, S.; Przuntek, H.; Epplen, J.T.; Schols, L.; Riess, O. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat. Genet., 1998, 18, 106-108.
8. Zarranz, J.J.; Alegre, J.; Gomez-Esteban, J.C.; Lezcano, E.; Ros, R.; Ampuero, I.; Vidal, L.; Hoenicka, J.; Rodriguez, O.; Atares, B.; Llorens, V.; Gomez Tortosa, E.; del Ser, T.; Munoz, D.G.; de Yebenes, J.G. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann. Neurol., 2004, 55, 164-173.
9. Satake, W.; Nakabayashi, Y.; Mizuta, I.; Hirota, Y.; Ito, C.; Kubo, M.; Kawaguchi, T.; Tsunoda, T.; Watanabe, M.; Takeda, A.; Tomiyama, H.; Nakashima, K.; Hasegawa, K.; Obata, F.; Yoshikawa, T.; Kawakami, H.; Sakoda, S.; Yamamoto, M.; Hattori, N.; Murata, M.; Nakamura, Y.; Toda, T. Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nat. Genet., 2009, 41, 1303-1307.
10. Simon-Sanchez, J.; Schulte, C.; Bras, J.M.; Sharma, M.; Gibbs, J.R.; Berg, D.; Paisan-Ruiz, C.; Lichtner, P.; Scholz, S.W.; Hernandez, D.G.; Kruger, R.; Federoff, M.; Klein, C.; Goate, A.; Perlmutter, J.; Bonin, M.; Nalls, M.A.; Illig, T.; Gieger, C.; Houlden, H.; Steffens, M.; Okun, M.S.; Racette, B.A.; Cookson, M.R.; Foote, K.D.; Fernandez, H.H.; Traynor, B.J.; Schreiber, S.; Arepalli, S.; Zonozi, R.; Gwinn, K.; van der Brug, M.; Lopez, G.; Chanock, S.J.; Schatzkin, A.; Park, Y.; Hollenbeck, A.; Gao, J.; Huang, X.; Wood, N.W.; Lorenz, D.; Deuschl, G.; Chen, H.; Riess, O.; Hardy, J.A.; Singleton, A.B.; Gasser, T. Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat. Genet., 2009, 41, 1308-1312.
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 alphasynuclein mice: implications for neurodegenerative disorders. Science, 2000, 287, 1265-1269.
12. Clayton, D.F.; George, J.M. Synucleins in synaptic plasticity and neurodegenerative disorders. J. Neurosci. Res., 1999, 58, 120-129.
13. Buchman, V.L.; Hunter, H.J.; Pinon, L.G.; Thompson, J.; Privalova, E.M.; Ninkina, N.N.; Davies, A.M. Persyn, a member of the synuclein family, has a distinct pattern of expression in the developing nervous system. J. Neurosci., 1998, 18, 9335-9341.
14. Giasson, B.I.; Murray, I.V.; Trojanowski, J.Q.; Lee, V.M. A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly. J. Biol. Chem., 2001, 276, 2380-2386.
15. Uversky, V.N., Fink, A. L. Amino acid determinants of alphasynuclein aggregation: putting together pieces of the puzzle. FEBS Lett., 2002, 522, 9-13.
16. Hashimoto, M.; Rockenstein, E.; Mante, M.; Mallory, M.; Masliah, E. Beta-synuclein inhibits alpha-synuclein aggregation: a possible role as an anti-parkinsonian factor. Neuron, 2001, 32, 213-223.
17. Hashimoto, M.; Rockenstein, E.; Mante, M.; Crews, L.; Bar-On, P.; Gage, F.H.; Marr, R.; Masliah, E. An antiaggregation gene therapy strategy for Lewy body disease utilizing beta-synuclein lentivirus in a transgenic model. Gene Ther., 2004, 11, 1713-1723.
18. Lotharius, J.; Brundin, P. Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein. Nat. Rev. Neurosci., 2002, 3, 932-942.
19. Chandra, S.; Gallardo, G.; Fernandez-Chacon, R.; Schluter, O.M.; Sudhof, T.C. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell, 2005, 123, 383-396.
20. Burre, J.; Sharma, M.; Tsetsenis, T.; Buchman, V.; Etherton, M.R.; Sudhof, T.C. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science, 2010, 329, 1663-1667.
21. Bussell, R., Jr.; Eliezer, D. A structural and functional role for 11- mer repeats in alpha-synuclein and other exchangeable lipid binding proteins. J. Mol. Biol., 2003, 329, 763-778.
22. Chandra, S.; Chen, X.; Rizo, J.; Jahn, R.; Sudhof, T.C. A broken alpha-helix in folded alpha-synuclein. J. Biol. Chem., 2003, 278, 15313-15318.
23. Davidson, W.S.; Jonas, A.; Clayton, D.F.; George, J.M. Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J. Biol. Chem., 1998, 273, 9443-9449.
24. Jao, C.C.; Der-Sarkissian, A.; Chen, J.; Langen, R. Structure of membrane-bound alpha-synuclein studied by site-directed spin labeling. Proc. Natl. Acad. Sci. USA, 2004, 101, 8331-8336.
25. Crowther, R.A.; Jakes, R.; Spillantini, M.G.; Goedert, M. Synthetic filaments assembled from C-terminally truncated alpha-synuclein. FEBS Lett., 1998, 436, 309-312.
26. Fernandez, C.O.; Hoyer, W.; Zweckstetter, M.; Jares-Erijman, E.A.; Subramaniam, V.; Griesinger, C.; Jovin, T.M. NMR of alphasynuclein- polyamine complexes elucidates the mechanism and kinetics of induced aggregation. EMBO J., 2004, 23, 2039-2046.
27. Hoyer, W.; Cherny, D.; Subramaniam, V.; Jovin, T.M. Impact of the acidic C-terminal region comprising amino acids 109-140 on alpha-synuclein aggregation in vitro. Biochemistry, 2004, 43, 16233-16242.
28. Ding, T.T.; Lee, S.J.; Rochet, J.C.; Lansbury, P.T., Jr. Annular alpha-synuclein protofibrils are produced when spherical protofibrils are incubated in solution or bound to brain-derived membranes. Biochemistry, 2002, 41, 10209-10217.
29. Lashuel, H.A.; Hartley, D.; Petre, B.M.; Walz, T.; Lansbury, P.T., Jr. Neurodegenerative disease: amyloid pores from pathogenic mutations. Nature, 2002, 418, 291-292.
30. Lashuel, H.A.; Petre, B.M.; Wall, J.; Simon, M.; Nowak, R.J.; Walz, T.; Lansbury, P.T., Jr. Alpha-synuclein, especially the Parkinson's disease-associated mutants, forms pore-like annular and tubular protofibrils. J. Mol. Biol., 2002, 322, 1089-1102.
31. Caughey, B.; Lansbury, P.T. Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. Annu. Rev. Neurosci., 2003, 26, 267-298.
32. Haass, C.; Steiner, H. Protofibrils, the unifying toxic molecule of neurodegenerative disorders? Nat. Neurosci., 2001, 4, 859-860.
33. Lansbury, P.T., Jr. Evolution of amyloid: what normal protein folding may tell us about fibrillogenesis and disease. Proc. Natl. Acad. Sci. USA, 1999, 96, 3342-3344.
34. Dyson, H.J.; Wright, P.E. Nuclear magnetic resonance methods for elucidation of structure and dynamics in disordered states. Methods Enzymol., 2001, 339, 258-270.
35. Dyson, H.J.; Wright, P.E. Insights into the structure and dynamics of unfolded proteins from nuclear magnetic resonance. Adv. Protein Chem., 2002, 62, 311-340.
36. Dyson, H.J.; Wright, P.E. Unfolded proteins and protein folding studied by NMR. Chem. Rev., 2004, 104, 3607-3622.
37. Dyson, H.J.; Wright, P.E. Elucidation of the protein folding landscape by NMR. Methods Enzymol., 2005, 394, 299-321.
38. 15N NMR spectroscopy. J. Mol. Biol., 1999, 288, 705-723.
39. 15N doubly-labeled flexible polypeptides: application to the human prion protein hPrP(23-230). J. Biomol. NMR, 2000, 16, 127-138.
40. Zhang, O.; Forman-Kay, J.D.; Shortle, D.; Kay, L.E. Tripleresonance NOESY-based experiments with improved spectral resolution: applications to structural characterization of unfolded, partially folded and folded proteins. J. Biomol. NMR, 1997, 9, 181-200.
41. 15Nrandom coil chemical shifts. J. Am. Chem. Soc., 1994, 116, 8466-8469.
42. Schwarzinger, S.; Kroon, G.J.; Foss, T.R.; Chung, J.; Wright, P.E.; Dyson, H.J. Sequence-dependent correction of random coil NMR chemical shifts. J. Am. Chem. Soc., 2001, 123, 2970-2978.
43. 15N random coil NMR chemical shifts of the common amino acids. Investigations of nearest-neighbor effects. J. Biomol. NMR, 1995, 5, 67-81.
44. Yao, J.; Dyson, H.J.; Wright, P.E. Chemical shift dispersion and secondary structure prediction in unfolded and partly folded proteins. FEBS Lett., 1997, 419, 285-289.
45. 15N spectra of proteins: heteronuclear triple-resonance three-dimensional NMR spectroscopy. Application to calmodulin. Biochemistry, 1990, 29, 4659-4667.
46. Bussell, R., Jr.; Eliezer, D. Residual structure and dynamics in Parkinson's disease-associated mutants of alpha-synuclein. J. Biol. Chem., 2001, 276, 45996-46003.
47. Bhavesh, N.S.; Panchal, S.C.; Hosur, R.V. An efficient highthroughput resonance assignment procedure for structural genomics and protein folding research by NMR. Biochemistry, 2001, 40, 14727-14735.
48. 15N) labeled proteins: application to unfolded proteins. J. Biomol. NMR, 2001, 20, 135-147.
49. Bermel, W.; Bertini, I.; Felli, I.C.; Lee, Y.M.; Luchinat, C.; Pierattelli, R. Protonless NMR experiments for sequence-specific assignment of backbone nuclei in unfolded proteins. J. Am. Chem. Soc., 2005, 128, 2.
50. Hsu, S.T.; Bertoncini, C.W.; Dobson, C.M. Use of protonless NMR spectroscopy to alleviate the loss of information resulting from exchange-broadening. J. Am. Chem. Soc., 2009, 131, 7222-7223.
51. Wang, Y.; Jardetzky, O. Probability-based protein secondary structure identification using combined NMR chemical-shift data. Protein Sci., 2002, 11, 852-861.
52. 15N chemical shift referencing in biomolecular NMR. J. Biomol. NMR, 1995, 6, 135-140.
53. Wishart, D.S.; Sykes, B.D.; Richards, F.M. The chemical shift index: a fast and simple method for the assignment of protein secondary structure through NMR spectroscopy. Biochemistry, 1992, 31, 1647-1651.
54. Bertoncini, C.W.; Rasia, R.M.; Lamberto, G.R.; Binolfi, A.; Zweckstetter, M.; Griesinger, C.; Fernandez, C.O. Structural characterization of the intrinsically unfolded protein betasynuclein, a natural negative regulator of alpha-synuclein aggregation. J. Mol. Biol., 2007, 372, 708-722.
55. Eliezer, D.; Kutluay, E.; Bussell, R., Jr.; Browne, G. Conformational properties of alpha-synuclein in its free and lipidassociated states. J. Mol. Biol., 2001, 307, 1061-1073.
56. Rospigliosi, C.C.; McClendon, S.; Schmid, A.W.; Ramlall, T.F.; Barre, P.; Lashuel, H.A.; Eliezer, D. E46K Parkinson's-linked mutation enhances C-terminal-to-N-terminal contacts in alphasynuclein. J. Mol. Biol., 2009, 388, 1022-1032.
57. Sung, Y.H.; Eliezer, D. Residual structure, backbone dynamics, and interactions within the synuclein family. J. Mol. Biol., 2007, 372, 689-707.
58. Marsh, J.A.; Singh, V.K.; Jia, Z.; Forman-Kay, J.D. Sensitivity of secondary structure propensities to sequence differences between alpha- and gamma-synuclein: implications for fibrillation. Protein Sci., 2006, 15, 2795-2804.
59. Serrano, L. Comparison between the phi distribution of the amino acids in the protein database and NMR data indicates that amino acids have various phi propensities in the random coil conformation. J. Mol. Biol., 1995, 254, 322-333.
60. Smith, L.J.; Bolin, K.A.; Schwalbe, H.; MacArthur, M.W.; Thornton, J.M.; Dobson, C.M. Analysis of main chain torsion angles in proteins: prediction of NMR coupling constants for native and random coil conformations. J. Mol. Biol., 1996, 255, 494-506.
61. Gillespie, J.R.; Shortle, D. Characterization of long-range structure in the denatured state of staphylococcal nuclease. I. Paramagnetic relaxation enhancement by nitroxide spin labels. J. Mol. Biol., 1997, 268, 158-169.
62. Kosen, P.A. Spin labeling of proteins. Methods Enzymol., 1989, 177, 86-121.
63. Bertoncini, C.W.; Jung, Y.S.; Fernandez, C.O.; Hoyer, W.; Griesinger, C.; Jovin, T.M.; Zweckstetter, M. Release of longrange tertiary interactions potentiates aggregation of natively unstructured alpha-synuclein. Proc. Natl. Acad. Sci. USA, 2005, 102, 1430-1435.
64. Dedmon, M.M.; Lindorff-Larsen, K.; Christodoulou, J.; Vendruscolo, M.; Dobson, C.M. Mapping long-range interactions in alpha-synuclein using spin-label NMR and ensemble molecular dynamics simulations. J. Am. Chem. Soc., 2005, 127, 476-477.
65. Allison, J.R.; Varnai, P.; Dobson, C.M.; Vendruscolo, M. Determination of the free energy landscape of alpha-synuclein using spin label nuclear magnetic resonance measurements. J. Am. Chem. Soc., 2009, 131, 18314-18326.
66. Bertoncini, C.W.; Fernandez, C.O.; Griesinger, C.; Jovin, T.M.; Zweckstetter, M. Familial mutants of alpha-synuclein with increased neurotoxicity have a destabilized conformation. J. Biol. Chem., 2005, 280, 30649-30652.
67. Wu, K.P.; Kim, S.; Fela, D.A.; Baum, J. Characterization of conformational and dynamic properties of natively unfolded human and mouse alpha-synuclein ensembles by NMR: implication for aggregation. J. Mol. Biol., 2008, 378, 1104-1115.
68. Kim, H.Y.; Heise, H.; Fernandez, C.O.; Baldus, M.; Zweckstetter, M. Correlation of amyloid fibril beta-structure with the unfolded state of alpha-synuclein. Chembiochem, 2007, 8, 1671-1674.
69. Paleologou, K.E.; Schmid, A.W.; Rospigliosi, C.C.; Kim, H.Y.; Lamberto, G.R.; Fredenburg, R.A.; Lansbury, P.T., Jr.; Fernandez, C.O.; Eliezer, D.; Zweckstetter, M.; Lashuel, H.A. Phosphorylation at Ser-129 but not the phosphomimics S129E/D inhibits the fibrillation of alpha-synuclein. J. Biol. Chem., 2008, 283, 16895-16905.
70. Paleologou, K.E.; Oueslati, A.; Shakked, G.; Rospigliosi, C.C.; Kim, H.Y.; Lamberto, G.R.; Fernandez, C.O.; Schmid, A.; Chegini, F.; Gai, W.P.; Chiappe, D.; Moniatte, M.; Schneider, B.L.; Aebischer, P.; Eliezer, D.; Zweckstetter, M.; Masliah, E.; Lashuel, H.A. Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synucleinmembrane interactions. J. Neurosci., 2010, 30, 3184-3198.
71. Cho, M.K.; Nodet, G.; Kim, H.Y.; Jensen, M.R.; Bernado, P.; Fernandez, C.O.; Becker, S.; Blackledge, M.; Zweckstetter, M. Structural characterization of alpha-synuclein in an aggregation prone state. Protein Sci., 2009, 18, 1840-1846.
72. McClendon, S.; Rospigliosi, C.C.; Eliezer, D. Charge neutralization and collapse of the C-terminal tail of alpha-synuclein at low pH. Protein Sci., 2009, 18, 1531-1540.
73. Wu, K.P.; Weinstock, D.S.; Narayanan, C.; Levy, R.M.; Baum, J. Structural reorganization of alpha-synuclein at low pH observed by NMR and REMD simulations. J. Mol. Biol., 2009, 391, 784-796.
74. Tjandra, N.; Bax, A. Direct measurement of distances and angles in biomolecules by NMR in a dilute liquid crystalline medium. Science, 1997, 278, 1111-1114.
75. Clore, G.M.; Starich, M.R.; Gronenborn, A.M. Measurement of residual dipolar couplings of macromolecules aligned in the nematic phase of a colloidal suspension of rod-shaped viruses. J. Am. Chem. Soc., 1998, 120, 10571-10572.
76. Alexandrescu, A.T.; Kammerer, R.A. Structure and disorder in the ribonuclease S-peptide probed by NMR residual dipolar couplings. Prot. Sci., 2003, 12, 2132-2140.
77. Otting, G.; Ruckert, M.; Levitt, M.H.; Moshref, A. NMR experiments for the sign determination of homonuclear scalar and residual dipolar couplings. J. Biomol. NMR, 2000, 16, 343-346.
78. Sass, H.J.; Musco, G.; Stahl, S.J.; Wingfield, P.T.; Grzesiek, S. Solution NMR of proteins within polyacrylamide gels: diffusional properties and residual alignment by mechanical stress or embedding of oriented purple membranes. J. Biomol. NMR, 2000, 18, 303-309.
79. Al-Hashimi, H.M.; Valafar, H.; Terrell, M.; Zartler, E.R.; Eidsness, M.K.; Prestegard, J.H. Variation of molecular alignment as a means of resolving orientational ambiguities in protein structures from dipolar couplings. J. Magn. Res., 2000, 143, 402-406.
80. Hudson, B.P.; Martinez-Yamout, M.A.; Dyson, H.J.; Wright, P.E. Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d. Nat. Struct. Mol. Biol., 2004, 11, 257-264.
81. Tsui, V.; Zhu, L.; Huang, T.H.; Wright, P.E.; Case, D.A. Assessment of zinc finger orientations by residual dipolar coupling constants. J. Biomol. NMR, 2000, 16, 9-21.
82. Al-Hashimi, H.M. Structural biology: Aerial view of the HIV genome. Nature, 2009, 460, 696-698.
83. Lange, O.F.; Lakomek, N.A.; Fares, C.; Schroder, G.F.; Walter, K.F.; Becker, S.; Meiler, J.; Grubmuller, H.; Griesinger, C.; de Groot, B.L. Recognition dynamics up to microseconds revealed from an RDC-derived ubiquitin ensemble in solution. Science, 2008, 320, 1471-1475.
84. Fieber, W.; Kristjansdottir, S.; Poulsen, F.M. Short-range, longrange and transition state interactions in the denatured state of ACBP from residual dipolar couplings. J. Mol. Biol., 2004, 339, 1191-1199.
85. Mohana-Borges, R.; Goto, N.K.; Kroon, G.J.; Dyson, H.J.; Wright, P.E. Structural characterization of unfolded states of apomyoglobin using residual dipolar couplings. J. Mol. Biol., 2004, 340, 1131-1142.
86. Shortle, D.; Ackerman, M.S. Persistence of native-like topology in a denatured protein in 8 M urea. Science, 2001, 293, 487-489.
87. Yang, W.Y.; Gruebele, M. Folding at the speed limit. Nature, 2003, 423, 193-197.
88. Salmon, L.; Nodet, G.; Ozenne, V.; Yin, G.; Jensen, M.R.; Zweckstetter, M.; Blackledge, M. NMR characterization of longrange order in intrinsically disordered proteins. J. Am. Chem. Soc., 2010, 132, 8407-8418.
89. Cho, M.K.; Kim, H.Y.; Bernado, P.; Fernandez, C.O.; Blackledge, M.; Zweckstetter, M. Amino acid bulkiness defines the local conformations and dynamics of natively unfolded alpha-synuclein and tau. J. Am. Chem. Soc., 2007, 129, 3032-3033.
90. Bernado, P.; Bertoncini, C.W.; Griesinger, C.; Zweckstetter, M.; Blackledge, M. Defining long-range order and local disorder in native alpha-synuclein using residual dipolar couplings. J. Am. Chem. Soc., 2005, 127, 17968-17969.
91. Binolfi, A.; Rasia, R.M.; Bertoncini, C.W.; Ceolin, M.; Zweckstetter, 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, 9893-9901.
92. Wilkins, D.K.; Grimshaw, S.B.; Receveur, V.; Dobson, C.M.; Jones, J.A.; Smith, L.J. Hydrodynamic radii of native and denatured proteins measured by pulse field gradient NMR techniques. Biochemistry, 1999, 38, 16424-16431.
93. Altieri, A.S.; Hinton, D.P.; Byrd, R.A. Association of biomolecular systems via pulsed-field gradient NMR self-diffusion measurements. J. Am. Chem. Soc., 1995, 117, 7566-7567.
94. Jones, J.A.; Wilkins, D.K.; Smith, L.J.; Dobson, C.M. Characterization of protein unfolding by NMR diffusion measurements. J. Biomol. NMR, 1997, 10, 199-203.
95. Pan, H.; Barany, G.; Woodward, G. Reduced BPTI is collapsed. A pulsed field gradient NMR study of unfolded and partially folded bovine pancreatic trypsin inhibitor. Protein Sci., 1997, 6, 1985-1992.
96. Uversky, V.N.; Li, J.; Fink, A.L. Evidence for a partially folded intermediate in alpha-synuclein fibril formation. J. Biol. Chem., 2001, 276, 10737-10744.
97. Uversky, V.N.; Li, J.; Fink, A.L. Metal-triggered structural transformations, aggregation, and fibrillation of human alphasynuclein. A possible molecular NK between Parkinson's disease and heavy metal exposure. J. Biol. Chem., 2001, 276, 44284-44296.
98. Serpell, L.C.; Sunde, M.; Benson, M.D.; Tennent, G.A.; Pepys, M.B.; Fraser, P.E. The protofilament substructure of amyloid fibrils. J. Mol. Biol., 2000, 300, 1033-1039.
99. Blake, C.; Serpell, L. Synchrotron X-ray studies suggest that the core of the transthyretin amyloid fibril is a continuous beta-sheet helix. Structure, 1996, 4, 989-998.
100. Fraser, P.E.; Nguyen, J.T.; Inouye, H.; Surewicz, W.K.; Selkoe, D.J.; Podlisny, M.B.; Kirschner, D.A. Fibril formation by primate, rodent, and Dutch-hemorrhagic analogues of Alzheimer amyloid beta-protein. Biochemistry, 1992, 31, 10716-10723.
101. Nielsen, J.T.; Bjerring, M.; Jeppesen, M.D.; Pedersen, R.O.; Pedersen, J.M.; Hein, K.L.; Vosegaard, T.; Skrydstrup, T.; Otzen, D.E.; Nielsen, N.C. Unique identification of supramolecular structures in amyloid fibrils by solid-state NMR spectroscopy. Angew Chem. Int. Ed. Engl., 2009, 48, 2118-2121.
102. Petkova, A.T.; Leapman, R.D.; Guo, Z.; Yau, W.M.; Mattson, M.P.; Tycko, R. Self-propagating, molecular-level polymorphism in Alzheimer's beta-amyloid fibrils. Science, 2005, 307, 262-265.
103. Tycko, R. Solid-state NMR as a probe of amyloid fibril structure. Curr. Opin. Chem. Biol., 2000, 4, 500-506.
104. Tycko, R. Insights into the amyloid folding problem from solidstate NMR. Biochemistry, 2003, 42, 3151-3159.
105. Tycko, R. Progress towards a molecular-level structural understanding of amyloid fibrils. Curr. Opin. Struct. Biol., 2004, 14, 96-103.
106. Laws, D.D.; Bitter, H.M.; Liu, K.; Ball, H.L.; Kaneko, K.; Wille, H.; Cohen, F.E.; Prusiner, S.B.; Pines, A.; Wemmer, D.E. Solidstate NMR studies of the secondary structure of a mutant prion protein fragment of 55 residues that induces neurodegeneration. Proc. Natl. Acad. Sci. USA, 2001, 98, 11686-11690.
107. Jaroniec, C.P.; MacPhee, C.E.; Bajaj, V.S.; McMahon, M.T.; Dobson, C.M.; Griffin, R.G. High-resolution molecular structure of a peptide in an amyloid fibril determined by magic angle spinning NMR spectroscopy. Proc. Natl. Acad. Sci. USA, 2004, 101, 711-716.
108. Siemer, A.B.; Ritter, C.; Ernst, M.; Riek, R.; Meier, B.H. Highresolution solid-state NMR spectroscopy of the prion protein HETs in its amyloid conformation. Angew Chem. Int. Ed. Engl., 2005, 44, 2441-2444.
109. Ferguson, N.; Becker, J.; Tidow, H.; Tremmel, S.; Sharpe, T.D.; Krause, G.; Flinders, J.; Petrovich, M.; Berriman, J.; Oschkinat, H.; Fersht, A.R. General structural motifs of amyloid protofilaments. Proc. Natl. Acad. Sci. USA, 2006, 103, 16248-16253.
110. Sillen, A.; Leroy, A.; Wieruszeski, J.M.; Loyens, A.; Beauvillain, J.C.; Buee, L.; Landrieu, I.; Lippens, G. Regions of tau implicated in the paired helical fragment core as defined by NMR. Chembiochem, 2005, 6, 1849-1856.
111. Petkova, A.T.; Ishii, Y.; Balbach, J.J.; Antzutkin, O.N.; Leapman, R.D.; Delaglio, F.; Tycko, R. A structural model for Alzheimer's beta-amyloid fibrils based on experimental constraints from solid state NMR. Proc. Natl. Acad. Sci. USA, 2002, 99, 16742-16747.
112. Siemer, A.B.; Arnold, A.A.; Ritter, C.; Westfeld, T.; Ernst, M.; Riek, R.; Meier, B.H. Observation of highly flexible residues in amyloid fibrils of the HET-s prion. J. Am. Chem. Soc., 2006, 128, 13224-13228.
113. Siemer, A.B.; Ritter, C.; Steinmetz, M.O.; Ernst, M.; Riek, R.; Meier, B.H. 13C, 15N resonance assignment of parts of the HET-s prion protein in its amyloid form. J. Biomol. NMR, 2006, 34, 75-87.
114. Ritter, C.; Maddelein, M.L.; Siemer, A.B.; Luhrs, T.; Ernst, M.; Meier, B.H.; Saupe, S.J.; Riek, R. Correlation of structural elements and infectivity of the HET-s prion. Nature, 2005, 435, 844-848.
115. Heise, H.; Hoyer, W.; Becker, S.; Andronesi, O.C.; Riedel, D.; Baldus, M. Molecular-level secondary structure, polymorphism, and dynamics of full-length alpha-synuclein fibrils studied by solid-state NMR. Proc. Natl. Acad. Sci. USA, 2005, 102, 6.
116. Miake, H.; Mizusawa, H.; Iwatsubo, T.; Hasegawa, M. Biochemical characterization of the core structure of alphasynuclein filaments. J. Biol. Chem., 2002, 277, 19213-19219.
117. Der-Sarkissian, A.; Jao, C.C.; Chen, J.; Langen, R. Structural organization of alpha-synuclein fibrils studied by site-directed spin labeling. J. Biol. Chem., 2003, 278, 37530-37535.
118. Kloepper, K.D.; Hartman, K.L.; Ladror, D.T.; Rienstra, C.M. Solid-state NMR spectroscopy reveals that water is nonessential to the core structure of alpha-synuclein fibrils. J. Phys. Chem. B, 2007, 111, 13353-13356.
119. Kloepper, K.D.; Zhou, D.H.; Li, Y.; Winter, K.A.; George, J.M.; Rienstra, C.M. Temperature-dependent sensitivity enhancement of solid-state NMR spectra of alpha-synuclein fibrils. J. Biomol. NMR, 2007, 39, 197-211.
120. Vilar, M.; Chou, H.T.; Lührs, T.; Maji, S.K.; Riek-Loher, D.; Verel, R.; Manning, G.; Stahlberg, H.; Riek, R. The fold of alphasynuclein fibrils. Proc. Natl. Acad. Sci. USA, 2008, 105, 8637-8642.
121. Heise, H.; Celej, M.S.; Becker, S.; Riedel, D.; Pelah, A.; Kumar, A.; Jovin, T.M.; Baldus, M. Solid-state NMR reveals structural differences between fibrils of wild-type and disease-related A53T mutant alpha-synuclein. J. Mol. Biol., 2008, 380, 444-450.
122. Kuwata, K.; Matumoto, T.; Cheng, H.; Nagayama, K.; James, T.L.; Roder, H. NMR-detected hydrogen exchange and molecular dynamics simulations provide structural insight into fibril formation of prion protein fragment 106-126. Proc. Natl. Acad. Sci. USA, 2003, 100, 14790-14795.
123. Whittemore, N.A.; Mishra, R.; Kheterpal, I.; Williams, A.D.; Wetzel, R.; Serpersu, E.H. Hydrogen-deuterium (H/D) exchange mapping of Abeta 1-40 amyloid fibril secondary structure using nuclear magnetic resonance spectroscopy. Biochemistry, 2005, 44, 4434-4441.
124. Luhrs, T.; Ritter, C.; Adrian, M.; Riek-Loher, D.; Bohrmann, B.; Dobeli, H.; Schubert, D.; Riek, R. 3D structure of Alzheimer's amyloid-beta(1-42) fibrils. Proc. Natl. Acad. Sci. USA, 2005, 102, 17342-17347.
125. Kim, H.Y.; Cho, M.K.; Riedel, D.; Fernandez, C.O.; Zweckstetter, M. Dissociation of amyloid fibrils of alpha-synuclein in supercooled water. Angew Chem. Int. Ed. Engl., 2008, 47, 5046-5048.
126. Kim, H.Y.; Cho, M.K.; Kumar, A.; Maier, E.; Siebenhaar, C.; Becker, S.; Fernandez, C.O.; Lashuel, H.A.; Benz, R.; Lange, A.; Zweckstetter, M. Structural properties of pore-forming oligomers of alpha-synuclein. J. Am. Chem. Soc., 2009, 131, 17482-17489.
127. Rochet, J.C.; Lansbury, P.T., Jr. Amyloid fibrillogenesis: themes and variations. Curr. Opin. Struct. Biol., 2000, 10, 60-68.
128. Cleary, J.P.; Walsh, D.M.; Hofmeister, J.J.; Shankar, G.M.; Kuskowski, M.A.; Selkoe, D.J.; Ashe, K.H. Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat. Neurosci., 2005, 8, 79-84.
129. Haass, C.; Selkoe, D.J. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid betapeptide. Nat. Rev. Mol. Cell Biol., 2007, 8, 101-112.
130. Bitan, G.; Teplow, D.B. Rapid photochemical cross-linking - A new tool for studies of metastable, amyloidogenic protein assemblies. Acc. Chem. Res., 2004, 37, 357-364.
131. 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.
132. 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, 1053-1065.
133. Foguel, D.; Suarez, M.C.; Ferrao-Gonzales, A.D.; Porto, T.C.; Palmieri, L.; Einsiedler, C.M.; Andrade, L.R.; Lashuel, H.A.; Lansbury, P.T.; Kelly, J.W.; Silva, J.L. Dissociation of amyloid fibrils of alpha-synuclein and transthyretin by pressure reveals their reversible nature and the formation of water-excluded cavities. Proc. Natl. Acad. Sci. USA, 2003, 100, 9831-9836.
134. Follmer, C.; Romao, L.; Einsiedler, C.M.; Porto, T.C.; Lara, F.A.; Moncores, M.; Weissmuller, G.; Lashuel, H.A.; Lansbury, P.; Neto, V.M.; Silva, J.L.; Foguel, D. Dopamine affects the stability, hydration, and packing of protofibrils and fibrils of the wild type and variants of alpha-synuclein. Biochemistry, 2007, 46, 472-482.
135. Kayed, R.; Head, E.; Thompson, J.L.; McIntire, T.M.; Milton, S.C.; Cotman, C.W.; Glabe, C.G. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science, 2003, 300, 486-489.
136. Karpinar, D.P.; Balija, M.B.; Kugler, S.; Opazo, F.; Rezaei-Ghaleh, N.; Wender, N.; Kim, H.Y.; Taschenberger, G.; Falkenburger, B.H.; Heise, H.; Kumar, A.; Riedel, D.; Fichtner, L.; Voigt, A.; Braus, G.H.; Giller, K.; Becker, S.; Herzig, A.; Baldus, M.; Jackle, H.; Eimer, S.; Schulz, J.B.; Griesinger, C.; Zweckstetter, M. Prefibrillar alpha-synuclein variants with impaired beta-structure increase neurotoxicity in Parkinson's disease models. EMBO J., 2009, 28, 3256-3268.
137. Wu, K.P.; Baum, J. Detection of transient interchain interactions in the intrinsically disordered protein alpha-synuclein by NMR paramagnetic relaxation enhancement. J. Am. Chem. Soc., 2010, 132, 5546-5547.
138. Iwahara, J.; Clore, M. Detecting transient intermediates in macromolecular binding by paramagnetic NMR. Nature, 2006, 440, 1227-1230.
139. Tang, C.; Iwahara, J.; Clore, G.M. Visualization of transient encounter complexes in protein-protein association. Nature, 2006, 444, 383-386.
140. Tang, C.; Louis, J.M.; Aniana, A.; Suh, J.Y.; Clore, G.M. Visualizing transient events in amino-terminal autoprocessing of HIV-1 protease. Nature, 2008, 455, 693-696.
141. Ulmer, T.S.; Bax, A. Comparison of structure and dynamics of micelle-bound human alpha-synuclein and Parkinson disease variants. J. Biol. Chem., 2005, 280, 43179-43187.
142. Ulmer, T.S.; Bax, A.; Cole, N.B.; Nussbaum, R.L. Structure and dynamics of micelle-bound human alpha-synuclein. J. Biol. Chem., 2005, 280, 9595-9603.
143. Borbat, P.; Ramlall, T.F.; Freed, J.H.; Eliezer, D. Inter-helix distances in lysophospholipid micelle-bound alpha-synuclein from pulsed ESR measurements. J. Am. Chem. Soc., 2006, 128, 10004-10005.
144. Rao, J.N.; Jao, C.C.; Hegde, B.G.; Langen, R.; Ulmer, T.S. A combinatorial NMR and EPR approach for evaluating the structural ensemble of partially folded proteins. J. Am. Chem. Soc., 2010, 132, 8657-8668.
145. Georgieva, E.R.; Ramlall, T.F.; Borbat, P.P.; Freed, J.H.; Eliezer, D. Membrane-bound alpha-synuclein forms an extended helix: long-distance pulsed ESR measurements using vesicles, bicelles, and rodlike micelles. J. Am. Chem. Soc., 2008, 130, 12856-12857.
146. Georgieva, E.R.; Ramlall, T.F.; Borbat, P.P.; Freed, J.H.; Eliezer, D. The lipid-binding domain of wild type and mutant alphasynuclein: compactness and interconversion between the broken and extended helix forms. J. Biol. Chem., 2010, 285, 28261-28274.
147. Bodner, C.R.; Dobson, C.M.; Bax, A. Multiple tight phospholipidbinding modes of alpha-synuclein revealed by solution NMR spectroscopy. J. Mol. Biol, 2009, 390, 775-790.
148. Bodner, C.R.; Maltsev, A.S.; Dobson, C.M.; Bax, A. Differential phospholipid binding of alpha-synuclein variants implicated in Parkinson's disease revealed by solution NMR spectroscopy. Biochemistry, 2010, 49, 862-871.
149. 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, offpathway oligomers. Nat. Struct. Mol. Biol., 2008, 15, 558-566.
150. Lamberto, G.R.; Binolfi, A.; Orcellet, M.L.; Bertoncini, C.W.; Zweckstetter, M.; Griesinger, C.; Fernandez, C.O. Structural and mechanistic basis behind the inhibitory interaction of PcTS on alpha-synuclein amyloid fibril formation. Proc. Natl. Acad. Sci. USA, 2009, 106, 21057-21062.