Exploring the accessible conformations of N-terminal acetylated α-synuclein

FEBS Letters

Volumn 587, Issue 8, 2013, Pages 1128-1138

  Moriarty, Gina M ^a   Janowska, Maria K ^a   Kang, Lijuan ^a   Baum, Jean ^a,b  

^a RUTGERS UNIVERSITY   (United States)

^b RUTGERS UNIVERSITY   (United States)

Author keywords

Keywords Synuclein Acetylation Aggregation Ensemble Fibril Fibril resistance Intrinsically disordered protein Oligomer Parkinson's disease

Indexed keywords

ALPHA SYNUCLEIN; MONOMER; TETRAMER;

ACETYLATION; ALZHEIMER DISEASE; AMINO TERMINAL SEQUENCE; FIBER; HUMAN; NEUROTOXICITY; NONHUMAN; OLIGOMERIZATION; PATHOGENICITY; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN PURIFICATION; REVIEW;

ACETYLATION; ALPHA-SYNUCLEIN; HUMANS; LEWY BODIES; PARKINSON DISEASE; PROTEIN CONFORMATION; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, SECONDARY;

EID: 84876065430     PISSN: 00145793     EISSN: 18733468     Source Type: Journal    
DOI: 10.1016/j.febslet.2013.02.049     Document Type: Review

References (174)

1. M.G. Spillantini, and M. Goedert The alpha-synucleinopathies: Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy Ann. N.Y. Acad. Sci. 920 2000 16 27
2. L. Stefanis Alpha-synuclein in Parkinson's disease Cold Spring Harb. Perspect. Med. 2 2012 a009399 10.1101/cshperspect.a009399
3. J.V. Hindle Ageing, neurodegeneration and Parkinson's disease Age Ageing 39 2010 156 161 10.1093/ageing/afp223
4. M.G. Spillantini, R.A. Crowther, R. Jakes, N.J. Cairns, P.L. Lantos, and M. Goedert Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson's disease and dementia with Lewy bodies Neurosci. Lett. 251 1998 205 208
5. M.G. Spillantini, R.A. Crowther, R. Jakes, M. Hasegawa, and M. Goedert Alpha-synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies Proc. Natl. Acad. Sci. USA 95 1998 6469 6473 10.1073/pnas.95.11.6469
6. L. Breydo, J.W. Wu, and V.N. Uversky α-Synuclein misfolding and Parkinson's disease Biochim. Biophys. Acta 1822 2012 261 285 10.1016/j.bbadis.2011.10.002
7. A.L. Fink The aggregation and fibrillation of alpha-synuclein Acc. Chem. Res. 39 2006 628 634 10.1021/Ar050073t
8. H.A. Lashuel, C.R. Overk, A. Oueslati, and E. Masliah The many faces of alpha-synuclein: from structure and toxicity to therapeutic target Nat. Rev. Neurosci. 14 2013 38 48 10.1038/Nrn3406
9. L. Maroteaux, J.T. Campanelli, and R.H. Scheller Synuclein - a neuron-specific protein localized to the nucleus and presynaptic nerve-terminal J. Neurosci. 8 1988 2804 2815
10. T. Shibayamaimazu, I. Okahashi, K. Omata, S. Nakajo, H. Ochiai, Y. Nakai, T. Hama, Y. Nakamura, and K. Nakaya Cell and tissue distribution and developmental-change of neuron-specific 14 kDa protein (phosphoneuroprotein-14) Brain Res. 622 1993 17 25 10.1016/0006-8993(93)90796-P
11. R. Jakes, M.G. Spillantini, and M. Goedert Identification of 2 distinct synucleins from human brain FEBS Lett. 345 1994 27 32 10.1016/0014-5793(94) 00395-5
12. A. Iwai, E. Masliah, M. Yoshimoto, N. Ge, L. Flanagan, H.A. de Silva, A. Kittel, and T. Saitoh The precursor protein of non-A beta component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system Neuron 14 1995 467 475
13. M. Bottner, D. Zorenkov, I. Hellwig, M. Barrenschee, J. Harde, T. Fricke, G. Deuschl, J.H. Egberts, T. Becker, and A. Fritscher-Ravens Expression pattern and localization of alpha-synuclein in the human enteric nervous system Neurobiol. Dis. 48 2012 474 480 10.1016/j.nbd.2012.07.018
14. R. Barbour, K. Kling, J.P. Anderson, K. Banducci, T. Cole, L. Diep, M. Fox, J.M. Goldstein, F. Soriano, and P. Seubert Red blood cells are the major source of alpha-synuclein in blood Neurodegener. Dis. 5 2008 55 59 10.1159/000112832
15. W.S. Davidson, A. Jonas, D.F. Clayton, and J.M. George Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes J. Biol. Chem. 273 1998 9443 9449 10.1074/jbc.273.16.9443
16. M. Bisaglia, I. Tessari, S. Mammi, and L. Bubacco Interaction between alpha-synuclein and metal ions, still looking for a role in the pathogenesis of Parkinson's disease Neuromolecular Med. 11 2009 239 251 10.1007/s12017-009-8082- 1
17. S. Chandra, G. Gallardo, R. Fernandez-Chacon, O.M. Schluter, and T.C. Sudhof Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration Cell 123 2005 383 396 10.1016/j.cell.2005.09.028
18. C.A. da Costa, K. Ancolio, and F. Checler Wild-type but not Parkinson's disease-related Ala-53 → Thr mutant alpha-synuclein protects neuronal cells from apoptotic stimuli J. Biol. Chem. 275 2000 24065 24069 10.1074/jbc. M002413200
19. D.D. Murphy, S.M. Rueter, J.Q. Trojanowski, and V.M.Y. Lee Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons J. Neurosci. 20 2000 3214 3220
20. K.K. Dev, K. Hofele, S. Barbieri, V.L. Buchman, and H. van der Putten Part II: Alpha-synuclein and its molecular pathophysiological role in neurodegenerative disease Neuropharmacology 45 2003 14 44
21. E. Maries, B. Dass, T.J. Collier, J.H. Kordower, and K. Steece-Collier The role of alpha-synuclein in Parkinson's disease: insights from animal models Nat. Rev. Neurosci. 4 2003 727 738 10.1038/Nrn1199
22. H. Jin, A. Kanthasamy, A. Ghosh, Y. Yang, V. Anantharam, and A.G. Kanthasamy Alpha-synuclein negatively regulates protein kinase Cdelta expression to suppress apoptosis in dopaminergic neurons by reducing p300 histone acetyltransferase activity J. Neurosci. 31 2011 2035 2051 10.1523/JNEUROSCI. 5634-10.2011
23. V.N. Uversky A protein-chameleon: conformational plasticity of alpha-synuclein, a disordered protein involved in neurodegenerative disorders J. Biomol. Struct. Dyn. 21 2003 211 234
24. V.N. Uversky, and A.L. Fink Conformational constraints for amyloid fibrillation: the importance of being unfolded Biochim. Biophys. Acta, Proteins Proteomics 1698 2004 131 153 10.1016/j.bbapap. 2003.12.008
25. T. Bartels, J.G. Choi, and D.J. Selkoe α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation Nature 477 2011 107 110 10.1038/nature10324
26. W. Wang, I. Perovic, J. Chittuluru, A. Kaganovich, L.T.T. Nguyen, J. Liao, J.R. Auclair, D. Johnson, A. Landeru, and A.K. Simorellis A soluble α-synuclein construct forms a dynamic tetramer Proc. Natl. Acad. Sci. 2011 10.1073/pnas.1113260108
27. A. Binolfi, F.X. Theillet, and P. Selenko Bacterial in-cell NMR of human alpha-synuclein: a disordered monomer by nature? Biochem. Soc. Trans. 40 2012 950-U292 10.1042/Bst20120096
28. B. Fauvet, M.B. Fares, F. Samuel, I. Dikiy, A. Tandon, D. Eliezer, and H.A. Lashuel Characterization of semisynthetic and naturally N-alpha-acetylated alpha-synuclein in vitro and in intact cells implications for aggregation and cellular properties of alpha-synuclein J. Biol. Chem. 287 2012 28243 28262 10.1074/jbc.M112.383711
29. B. Fauvet, M.K. Mbefo, M.-B. Fares, C. Desobry, S. Michael, M.T. Ardah, E. Tsika, P. Coune, M. Prudent, and N. Lion Alpha-synuclein in the central nervous system and from erythrocytes, mammalian cells and E. coli exists predominantly as a disordered monomer J. Biol. Chem. 287 2012 15345 15364 10.1074/jbc.M111.318949
30. L.J. Kang, G.M. Moriarty, L.A. Woods, A.E. Ashcroft, S.E. Radford, and J. Baum N-terminal acetylation of alpha-synuclein induces increased transient helical propensity and decreased aggregation rates in the intrinsically disordered monomer Protein Sci. 21 2012 911 917 10.1002/Pro.2088
31. A.S. Maltsev, J.F. Ying, and A. Bax Impact of N-terminal acetylation of alpha-synuclein on its random coil and lipid binding properties Biochemistry 51 2012 5004 5013 10.1021/Bi300642h
32. A.J. Trexler, and E. Rhoades N-terminal acetylation is critical for forming α-helical oligomer of α-synuclein Protein Sci. 21 2012 601 605 10.1002/Pro.2056
33. U. Dettmer, A.J. Newman, E.S. Luth, T. Bartels, and D. Selkoe In vivo crosslinking reveals principally oligomeric forms of alpha-synuclein and beta-synuclein in neurons and non-neural cells J. Biol. Chem. 2013 10.1074/jbc.M112.403311
34. P.H. Weinreb, W. Zhen, A.W. Poon, K.A. Conway, and P.T. Lansbury Jr. NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded Biochemistry 35 1996 13709 13715 10.1021/bi961799n
35. R. Bussell, and D. Eliezer A structural and functional role for 11-mer repeats in alpha-synuclein and other exchangeable lipid binding proteins J. Mol. Biol. 329 2003 763 778 10.1016/S0022-2836(03)00520-5
36. V.N. Uversky, J. Li, and A.L. Fink Evidence for a partially folded intermediate in alpha-synuclein fibril formation J. Biol. Chem. 276 2001 10737 10744 10.1074/jbc.M010907200
37. L.A. Munishkina, A.L. Fink, and V.N. Uversky Accelerated fibrillation of alpha-synuclein induced by the combined action of macromolecular crowding and factors inducing partial folding Curr. Alzheimer Res. 6 2009 252 260
38. K.P. Wu, D.S. Weinstock, C. Narayanan, R.M. Levy, and J. Baum Structural reorganization of alpha-synuclein at low pH observed by NMR and REMD simulations J. Mol. Biol. 391 2009 784 796 10.1016/j.jmb.2009.06.063
39. D.-P. Hong, W. Xiong, J.-Y. Chang, and C. Jiang The role of the C-terminus of human α-synuclein: intra-disulfide bonds between the C-terminus and other regions stabilize non-fibrillar monomeric isomers FEBS Lett. 585 2011 561 566 10.1016/j.febslet.2011.01.009
40. S.M. Park, H.Y. Jung, T.D. Kim, J.H. Park, C.H. Yang, and J. Kim Distinct roles of the N-terminal-binding domain and the C-terminal-solubilizing domain of alpha-synuclein, a molecular chaperone J. Biol. Chem. 277 2002 28512 28520 10.1074/jbc.M111971200
41. P.H. Weinreb, W.G. Zhen, A.W. Poon, K.A. Conway, and P.T. Lansbury NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded Biochemistry 35 1996 13709 13715 10.1021/bi961799n
42. B.I. Giasson, K. Uryu, J.Q. Trojanowski, and V.M.Y. Lee Mutant and wild type human alpha-synucleins assemble into elongated filaments with distinct morphologies in vitro J. Biol. Chem. 274 1999 7619 7622 10.1074/jbc.274.12.7619
43. J. Soppa Protein acetylation in archaea, bacteria, and eukaryotes Archaea (Vancouver, BC) 2010 2010 10.1155/2010/820681
44. V.N. Uversky Natively unfolded proteins: a point where biology waits for physics Protein Sci. 11 2002 739 756 10.1110/ps.4210102.matic
45. V.N. Uversky Use of fast protein size-exclusion liquid chromatography to study the unfolding of proteins which denature through the molten globule Biochemistry 32 1993 13288 13298
46. A.K. Dunker, J.D. Lawson, C.J. Brown, R.M. Williams, P. Romero, J.S. Oh, C.J. Oldfield, A.M. Campen, C.R. Ratliff, and K.W. Hipps Intrinsically disordered protein J. Mol. Graph. Model. 19 2001 26 59 10.1016/s1093-3263(00) 00138-8
47. D. Eliezer, E. Kutluay, R. Bussell, and G. Browne Conformational properties of alpha-synuclein in its free and lipid-associated states J. Mol. Biol. 307 2001 1061 1073
48. J.R. Allison, P. Varnai, C.M. Dobson, and M. Vendruscolo Determination of the free energy landscape of alpha-synuclein using spin label nuclear magnetic resonance measurements J. Am. Chem. Soc. 131 2009 18314 18326 10.1021/Ja904716h
49. L. Salmon, G. Nodet, V. Ozenne, G. Yin, M.R. Jensen, M. Zweckstetter, and M. Blackledge NMR characterization of long-range order in intrinsically disordered proteins J. Am. Chem. Soc. 132 2010 8407 8418 10.1021/ja101645g
50. C.W. Bertoncini, Y.S. Jung, C.O. Fernandez, W. Hoyer, C. Griesinger, T.M. Jovin, and M. Zweckstetter Release of long-range tertiary interactions potentiates aggregation of natively unstructured alpha-synuclein Proc. Natl. Acad. Sci. USA 102 2005 1430 1435 10.1073/pnas.0407146102
51. P. Bernado, C.W. Bertoncini, C. Griesinger, M. Zweckstetter, and M. Blackledge Defining long-range order and local disorder in native alpha-synuclein using residual dipolar couplings J. Am. Chem. Soc. 127 2005 17968 17969 10.1021/Ja055538p
52. M.M. Dedmon, K. Lindorff-Larsen, J. Christodoulou, M. Vendruscolo, and C.M. Dobson Mapping long-range interactions in alpha-synuclein using spin-label NMR and ensemble molecular dynamics simulations J. Am. Chem. Soc. 127 2005 476 477 10.1021/ja044834j
53. M.K. Cho, H.Y. Kim, P. Bernado, C.O. Fernandez, M. Blackledge, and M. Zweckstetter Amino acid bulkiness defines the local conformations and dynamics of natively unfolded alpha-synuclein and tau J. Am. Chem. Soc. 129 2007 3032 10.1021/Ja067482k
54. K.P. Wu, and J. Baum Detection of transient interchain interactions in the intrinsically disordered protein alpha-synuclein by NMR paramagnetic relaxation enhancement J. Am. Chem. Soc. 132 2010 5546 10.1021/Ja9105495
55. L. Kang, K.-P. Wu, M. Vendruscolo, and J. Baum The A53T mutation is key in defining the differences in the aggregation kinetics of human and mouse α-synuclein J. Am. Chem. Soc. 133 2011 13465 13470 10.1021/ja203979j
56. J.N. Rao, C.C. Jao, B.G. Hegde, R. Langen, and T.S. Ulmer A combinatorial NMR and EPR approach for evaluating the structural ensemble of partially folded proteins J. Am. Chem. Soc. 132 2010 8657 8668 10.1021/ja100646t
57. J.C. Lee, B.T. Lai, J.J. Kozak, H.B. Gray, and J.R. Winkler Alpha-synuclein tertiary contact dynamics J. Phys. Chem. B 111 2007 2107 2112 10.1021/jp068604y
58. M.K. Cho, G. Nodet, H.Y. Kim, M.R. Jensen, P. Bernado, C.O. Fernandez, S. Becker, M. Blackledge, and M. Zweckstetter Structural characterization of alpha-synuclein in an aggregation prone state Protein Sci. 18 2009 1840 1846 10.1002/Pro.194
59. R. Bussell, and D. Eliezer Residual structure and dynamics in Parkinson's disease-associated mutants of alpha-synuclein J. Biol. Chem. 276 2001 45996 46003 10.1074/jbc.M106777200
60. Y.-H. Sung, and D. Eliezer Residual structure, backbone dynamics, and interactions within the synuclein family J. Mol. Biol. 372 2008 689 707
61. C. Narayanan, D.S. Weinstock, K.P. Wu, J. Baum, and R.M. Levy Investigation of the polymeric properties of alpha-synuclein and comparison with NMR experiments: a replica exchange molecular dynamics study J. Chem. Theory Comput. 8 2012 3929 3942 10.1021/Ct300241t
62. H.J. Dyson, and P.E. Wright Intrinsically unstructured proteins and their functions Nat. Rev. Mol. Cell Biol. 6 2005 197 208 10.1038/nrm1589
63. W. Hoyer, D. Cherny, V. Subramaniam, and T.M. Jovin Impact of the acidic C-terminal region comprising amino acids 109-140 on alpha-synuclein aggregation in vitro Biochemistry 43 2004 16233 16242 10.1021/bi048453u
64. C.W. Bertoncini, Y.-S. Jung, C.O. Fernandez, W. Hoyer, C. Griesinger, T.M. Jovin, and M. Zweckstetter Release of long-range tertiary interactions potentiates aggregation of natively unstructured alpha-synuclein Proc. Natl. Acad. Sci. USA 102 2005 1430 1435 10.1073/pnas.0407146102
65. T.L. Yap, C.M. Pfefferkorn, and J.C. Lee Residue-specific fluorescent probes of alpha-synuclein: detection of early events at the N- and C-termini during fibril assembly Biochemistry 50 2011 1963 1965 10.1021/bi2000824
66. S. McClendon, C.C. Rospigliosi, and D. Eliezer Charge neutralization and collapse of the C-terminal tail of alpha-synuclein at low pH Protein Sci. 18 2009 1531 1540 10.1002/Pro.149
67. V.N. Uversky, J. Li, and A.L. Fink Evidence for a partially folded intermediate in alpha-synuclein fibril formation J. Biol. Chem. 276 2001 10737 10744 10.1074/jbc.M010907200
68. V.N. Uversky, J. Li, P. Souillac, I.S. Millett, S. Doniach, R. Jakes, M. Goedert, and A.L. Fink Biophysical properties of the synucleins and their propensities to fibrillate: inhibition of alpha-synuclein assembly by beta- and gamma-synucleins J. Biol. Chem. 277 2002 11970 11978 10.1074/jbc.M109541200
69. V.N. Uversky, H.-J.J. Lee, J. Li, A.L. Fink, and S.-J.J. Lee Stabilization of partially folded conformation during alpha-synuclein oligomerization in both purified and cytosolic preparations J. Biol. Chem. 276 2001 43495 43498 10.1074/jbc.C100551200
70. V.N. Uversky, J. Li, and A.L. Fink Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkinson's disease and heavy metal exposure J. Biol. Chem. 276 2001 44284 44296 10.1074/jbc.M105343200
71. V.N. Uversky, J. Li, and A.L. Fink Pesticides directly accelerate the rate of alpha-synuclein fibril formation: a possible factor in Parkinson's disease FEBS Lett. 500 2001 105 108 10.1016/S0014-5793(01)02597-2
72. V.N. Uversky, J. Li, K. Bower, and A.L. Fink Synergistic effects of pesticides and metals on the fibrillation of alpha-synuclein: implications for Parkinson's disease Neurotoxicology 23 2002 527 536 10.1016/S0161-813x(02)00067- 0
73. C.W. Bertoncini, C.O. Fernandez, C. Griesinger, T.M. Jovin, and M. Zweckstetter Familial mutants of alpha-synuclein with increased neurotoxicity have a destabilized conformation J. Biol. Chem. 280 2005 30649 30652 10.1074/jbc.C500288200
74. K.A. Conway, J.D. Harper, and P.T. Lansbury Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease Nat. Med. 4 1998 1318 1320 10.1038/3311
75. J. Li, V.N. Uversky, and A.L. Fink Effect of familial Parkinson's disease point mutations A30P and A53T on the structural properties, aggregation, and fibrillation of human alpha-synuclein Biochemistry 40 2001 11604 11613 10.1021/Bi010616g
76. J. Li, V.N. Uversky, and A.L. Fink Conformational behavior of human alpha-synuclein is modulated by familial Parkinson's disease point mutations A30P and A53T Neurotoxicology 23 2002 553 567 10.1016/S0161-813x(02)00066-9
77. O.M. El-Agnaf, R. Jakes, M.D. Curran, and A. Wallace Effects of the mutations Ala30 to Pro and Ala53 to Thr on the physical and morphological properties of alpha-synuclein protein implicated in Parkinson's disease FEBS Lett. 440 1998 67 70
78. E.A. Greenbaum, C.L. Graves, A.J. Mishizen-Eberz, M.A. Lupoli, D.R. Lynch, S.W. Englander, P.H. Axelsen, and B.I. Giasson The E46K mutation in alpha-synuclein increases amyloid fibril formation J. Biol. Chem. 280 2005 7800 7807 10.1074/jbc.M411638200
79. K.P. Wu, S. Kim, D.A. Fela, and J. Baum Characterization of conformational and dynamic properties of natively unfolded human and mouse alpha-synuclein ensembles by NMR: implication for aggregation J. Mol. Biol. 378 2008 1104 1115 10.1016/j.jmb.2008.03.017
80. R.A. Fredenburg, C. Rospigliosi, R.K. Meray, J.C. Kessler, H.A. Lashuel, D. Eliezer, and P.T. Lansbury The impact of the E46K mutation on the properties of alpha-synuclein in its monomeric and oligomeric states Biochemistry 46 2007 7107 7118 10.1021/Bi7000246
81. C.C. Rospigliosi, S. McClendon, A.W. Schmid, T.F. Ramlall, P. Barre, H.A. Lashuel, and D. Eliezer E46K Parkinson's-linked mutation enhances C-terminal-to-N-terminal contacts in alpha-synuclein J. Mol. Biol. 388 2009 1022 1032 10.1016/j.jmb.2009.03.065
82. T.S. Ulmer, A. Bax, N.B. Cole, and R.L. Nussbaum Structure and dynamics of micelle-bound human alpha-synuclein J. Biol. Chem. 280 2005 9595 9603 10.1074/jbc.M411805200
83. D. Eliezer, E. Kutluay, R. Bussell, and G. Browne Conformational properties of alpha-synuclein in its free and lipid-associated states J. Mol. Biol. 307 2001 1061 1073 10.1006/jmbi.2001.4538
84. T. Bartels, L.S. Ahlstrom, A. Leftin, F. Kamp, C. Haass, M.F. Brown, and K. Beyer The N-terminus of the intrinsically disordered protein alpha-synuclein triggers membrane binding and helix folding Biophys. J. 99 2010 2116 2124 10.1016/j.bpj.2010.06.035
85. D. Eliezer, E. Kutluay, R. Bussell Jr.; and G. Browne Conformational properties of alpha-synuclein in its free and lipid-associated states J. Mol. Biol. 307 2001 1061 1073 10.1006/jmbi.2001.4538
86. R.L. Croke, C.O. Sallum, E. Watson, E.D. Watt, and A.T. Alexandrescu Hydrogen exchange of monomeric alpha-synuclein shows unfolded structure persists at physiological temperature and is independent of molecular crowding in Escherichia coli Protein Sci. 17 2008 1434 1445 10.1110/ps.033803.107
87. A.J. Trexler, and E. Rhoades Alpha-synuclein binds large unilamellar vesicles as an extended helix Biochemistry 48 2009 2304 2306 10.1021/Bi900114z
88. C.C. Jao, B.G. Hegde, J. Chen, I.S. Haworth, and R. Langen Structure of membrane-bound alpha-synuclein from site-directed spin labeling and computational refinement Proc. Natl. Acad. Sci. USA 105 2008 19666 19671 10.1073/pnas.0807826105
89. T.S. Ulmer, A. Bax, N.B. Cole, and R.L. Nussbaum Structure and dynamics of micelle-bound human alpha-synuclein J. Biol. Chem. 280 2005 9595 9603 10.1074/jbc.M411805200
90. S.L. Bernstein, D.F. Liu, T. Wyttenbach, M.T. Bowers, J.C. Lee, H.B. Gray, and J.R. Winkler Alpha-synuclein: stable compact and extended monomeric structures and pH dependence of dimer formation J. Am. Soc. Mass Spectrom. 15 2004 1435 1443 10.1016/j.jasms.2004.08.003
91. A.K. Frimpong, R.R. Abzalimov, V.N. Uversky, and I.A. Kaltashov Characterization of intrinsically disordered proteins with electrospray ionization mass spectrometry: conformational heterogeneity of alpha-synuclein Proteins Struct. Funct. Bioinform. 78 2010 714 722 10.1002/prot.22604
92. M. Pivato, G. De Franceschi, L. Tosatto, E. Frare, D. Kumar, D. Aioanei, M. Brucale, I. Tessari, M. Bisaglia, and B. Samori Covalent α-synuclein dimers: chemico-physical and aggregation properties PLoS ONE 7 2012 e50027 10.1371/journal.pone.0050027
93. M.S. Celej, R. Sarroukh, E. Goormaghtigh, G.D. Fidelio, J.M. Ruysschaert, and V. Raussens Toxic prefibrillar alpha-synuclein amyloid oligomers adopt a distinctive antiparallel beta-sheet structure Biochem. J. 443 2012 719 726 10.1042/BJ20111924
94. V.N. Uversky, H.J. Lee, J. Li, A.L. Fink, and S.J. Lee Stabilization of partially folded conformation during alpha-synuclein oligomerization in both purified and cytosolic preparations J. Biol. Chem. 276 2001 43495 43498 10.1074/jbc.C100551200
95. S. Krishnan, E.Y. Chi, S.J. Wood, B.S. Kendrick, C. Li, W. Garzon-Rodriguez, J. Wypych, T.W. Randolph, L.O. Narhi, and A.L. Biere Oxidative dimer formation is the critical rate-limiting step for Parkinson's disease alpha-synuclein fibrillogenesis Biochemistry 42 2003 829 837 10.1021/bi026528t
96. W. Zhou, and C.R. Freed Tyrosine-to-cysteine modification of human alpha-synuclein enhances protein aggregation and cellular toxicity J. Biol. Chem. 279 2004 10128 10135 10.1074/jbc.M307563200
97. M.S. Goldberg, and P.T. Lansbury Is there a cause-and-effect relationship between alpha-synuclein fibrillization and Parkinson's disease? Nat. Cell Biol. 2 2000 E115 E119
98. K.A. Conway, S.J. Lee, J.C. Rochet, T.T. Ding, J.D. Harper, R.E. Williamson, and P.T. Lansbury Accelerated oligomerization by Parkinson's disease linked alpha-synuclein mutants Ann. N.Y. Acad. Sci. 920 2000 42 45
99. E. Masliah, E. Rockenstein, I. Veinbergs, M. Mallory, M. Hashimoto, A. Takeda, Y. Sagara, A. Sisk, and L. Mucke Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders Science 287 2000 1265 1269 10.1126/science.287.5456.1265
100. D.A.M. Amer, G.B. Irvine, and O.M.A. El-Agnaf Inhibitors of alpha-synuclein oligomerization and toxicity: a future therapeutic strategy for Parkinson's disease and related disorders Exp. Brain Res. 173 2006 223 233 10.1007/s00221-006-0539-y
101. R. Kayed, E. Head, J.L. Thompson, T.M. McIntire, S.C. Milton, C.W. Cotman, and C.G. Glabe Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis Science 300 2003 486 489 10.1126/science. 1079469
102. K.J. Wolfe, and D.M. Cyr Amyloid in neurodegenerative diseases: friend or foe? Semin. Cell Dev. Biol. 22 2011 476 481 10.1016/j.semcdb.2011.03.011
103. C. Haass, and D.J. Selkoe Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide Nat. Rev. Mol. Cell Biol. 8 2007 101 112 10.1038/nrm2101
104. B. Caughey, and P.T. Lansbury Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders Annu. Rev. Neurosci. 26 2003 267 298 10.1146/annurev.neuro. 26.010302.081142
105. C.M. Dobson Protein misfolding, evolution and disease Trends Biochem. Sci. 24 1999 329 332
106. E. Zerovnik Oligomerization preceding amyloid fibril formation: a process in common to intrinsically disordered and globular proteins Network 22 2011 154 161 10.3109/0954898X.2011.639842
107. J. Lee, E.K. Culyba, E.T. Powers, and J.W. Kelly Amyloid-β forms fibrils by nucleated conformational conversion of oligomers Nat. Chem. Biol. 7 2011 600 607 10.1038/nchembio.624
108. N. Cremades, S.I.A. Cohen, E. Deas, A.Y. Abramov, A.Y. Chen, A. Orte, M. Sandal, R.W. Clarke, P. Dunne, and F.A. Aprile Direct observation of the interconversion of normal and toxic forms of alpha-synuclein Cell 149 2012 1048 1059 10.1016/j.cell.2012.03.037
109. M.M. Apetri, N.C. Maiti, M.G. Zagorski, P.R. Carey, and V.E. Anderson Secondary structure of alpha-synuclein oligomers: characterization by raman and atomic force microscopy J. Mol. Biol. 355 2006 63 71 10.1016/j.jmb.2005.10.071
110. J.-H. Lee, I.-H. Lee, Y.-J. Choe, S. Kang, H.Y. Kim, W.-P. Gai, J.-S. Hahn, and S.R. Paik Real-time analysis of amyloid fibril formation of alpha-synuclein using a fibrillation-state-specific fluorescent probe of JC-1 Biochem. J. 418 2009 311 323 10.1042/BJ20081572
111. J. Gsponer, U. Haberthur, and A. Caflisch The role of side-chain interactions in the early steps of aggregation: molecular dynamics simulations of an amyloid-forming peptide from the yeast prion Sup35 Proc. Natl. Acad. Sci. USA 100 2003 5154 5159 10.1073/pnas.0835307100
112. M. Cheon, I. Chang, S. Mohanty, L.M. Luheshi, C.M. Dobson, M. Vendruscolo, and G. Favrin Structural reorganisation and potential toxicity of oligomeric species formed during the assembly of amyloid fibrils PLoS Comput. Biol. 3 2007 1727 1738 10.1371/journal.pcbi.0030173
113. A. Dusa, J. Kaylor, S. Edridge, N. Bodner, D.P. Hong, and A.L. Fink Characterization of oligomers during alpha-synuclein aggregation using intrinsic tryptophan fluorescence Biochemistry 45 2006 2752 2760 10.1021/Bi051426z
114. B. Bolognesi, J.R. Kumita, T.P. Barros, E.K. Esbjorner, L.M. Luheshi, D.C. Crowther, M.R. Wilson, C.M. Dobson, G. Favrin, and J.J. Yerbury ANS binding reveals common features of cytotoxic amyloid species ACS Chem. Biol. 5 2010 735 740 10.1021/cb1001203
115. T.F. Outeiro, P. Putcha, J.E. Tetzlaff, R. Spoelgen, M. Koker, F. Carvalho, B.T. Hyman, and P.J. McLean Formation of toxic oligomeric alpha-synuclein species in living cells PLoS ONE 3 2008 e1867 10.1371/journal.pone.0001867
116. S. Campioni, B. Mannini, M. Zampagni, A. Pensalfini, C. Parrini, E. Evangelisti, A. Relini, M. Stefani, C.M. Dobson, and C. Cecchi A causative link between the structure of aberrant protein oligomers and their toxicity Nat. Chem. Biol. 6 2010 140 147 10.1038/nchembio.283
117. R. Krishnan, J.L. Goodman, S. Mukhopadhyay, C.D. Pacheco, Ea Lemke, Aa Deniz, and S. Lindquist Conserved features of intermediates in amyloid assembly determine their benign or toxic states Proc. Natl. Acad. Sci. USA 109 2012 11172 11177 10.1073/pnas.1209527109
118. B. Winner, R. Jappelli, S.K. Maji, Desplats. Pa, L. Boyer, S. Aigner, C. Hetzer, T. Loher, M. Vilar, and S. Campioni In vivo demonstration that alpha-synuclein oligomers are toxic Proc. Natl. Acad. Sci. USA 108 2011 4194 4199 10.1073/pnas.1100976108
119. H.Y. Kim, M.K. Cho, A. Kumar, E. Maier, C. Siebenhaar, S. Becker, C.O. Fernandez, H.A. Lashuel, R. Benz, and A. Lange Structural properties of pore-forming oligomers of alpha-synuclein J. Am. Chem. Soc. 131 2009 17482 17489 10.1021/Ja9077599
120. I.F. Tsigelny, Y. Sharikov, W. Wrasidlo, T. Gonzalez, P.A. Desplats, L. Crews, B. Spencer, and E. Masliah Role of alpha-synuclein penetration into the membrane in the mechanisms of oligomer pore formation FEBS J. 279 2012 1000 1013 10.1111/j.1742-4658.2012.08489.x
121. K.M. Danzer, D. Haasen, A.R. Karow, S. Moussaud, M. Habeck, A. Giese, H. Kretzschmar, B. Hengerer, and M. Kostka Different species of alpha-synuclein oligomers induce calcium influx and seeding J. Neurosci. 27 2007 9220 9232 10.1523/Jneurosci.2617-07.2007
122. N.B. Cole, D.D. Murphy, T. Grider, S. Rueter, D. Brasaemle, and R.L. Nussbaum Lipid droplet binding and oligomerization properties of the Parkinson's disease protein alpha-synuclein J. Biol. Chem. 277 2002 6344 6352 10.1074/jbc.M108414200
123. K.A. Conway, S.J. Lee, J.C. Rochet, T.T. Ding, J.D. Harper, R.E. Williamson, and P.T. Lansbury Jr. Accelerated oligomerization by Parkinson's disease linked alpha-synuclein mutants Ann. N.Y. Acad. Sci. 920 2000 42 45
124. K.A. Conway, S.J. Lee, J.C. Rochet, T.T. Ding, R.E. Williamson, and P.T. Lansbury Jr. Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy Proc. Natl. Acad. Sci. USA 97 2000 571 576
125. H.A. Lashuel, B.M. Petre, J. Wall, M. Simon, R.J. Nowak, T. Walz, and P.T. Lansbury Alpha-synuclein, especially the Parkinson's disease-associated mutants, forms pore-like annular and tubular protofibrils J. Mol. Biol. 322 2002 1089 1102 10.1016/S0022-2836(02)00735-0
126. J. Kaylor, N. Bodner, S. Edridge, G. Yamin, D.-P. Hong, and A.L. Fink Characterization of oligomeric intermediates in α-synuclein fibrillation: FRET studies of Y125W/Y133F/Y136F alpha-synuclein J. Mol. Biol. 353 2005 357 372 10.1016/j.jmb.2005.08.046
127. T.T. Ding, S.J. Lee, J.C. Rochet, and P.T. Lansbury Annular alpha-synuclein protofibrils are produced when spherical protofibrils are incubated in solution or bound to brain-derived membranes Biochemistry 41 2002 10209 10217 10.1021/Bi020139h
128. D.L. Pountney, N.H. Voelcker, and W.P. Gai Annular alpha-synuclein oligomers are potentially toxic agents in alpha-synucleinopathy. Hypothesis Neurotox. Res. 7 2005 59 67
129. D.P. Hong, S. Han, A.L. Fink, and V.N. Uversky Characterization of the non-fibrillar alpha-synuclein oligomers Protein Pept. Lett. 18 2011 230 240
130. L.A. Munishkina, C. Phelan, V.N. Uversky, and A.L. Fink Conformational behavior and aggregation of alpha-synuclein in organic solvents: modeling the effects of membranes Biochemistry 42 2003 2720 2730 10.1021/bi027166s
131. J.M. Souza, B.I. Giasson, Q.P. Chen, V.M.Y. Lee, and H. Ischiropoulos Dityrosine cross-linking promotes formation of stable alpha-synuclein polymers - implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies J. Biol. Chem. 275 2000 18344 18349 10.1074/jbc.M000206200
132. V.N. Uversky, G. Yamin, Munishkina. La, Ma Karymov, I.S. Millett, S. Doniach, Y.L. Lyubchenko, and A.L. Fink Effects of nitration on the structure and aggregation of alpha-synuclein Brain Res. Mol. Brain Res. 134 2005 84 102 10.1016/j.molbrainres.2004.11.014
133. E.H. Norris, B.I. Giasson, H. Ischiropoulos, and V.M.Y. Lee Effects of oxidative and nitrative challenges on alpha-synuclein fibrillogenesis involve distinct mechanisms of protein modifications J. Biol. Chem. 278 2003 27230 27240 10.1074/jbc.M212436200
134. R. Hodara, E.H. Norris, B.I. Giasson, A.J. Mishizen-Eberz, D.R. Lynch, V.M.-Y.M.-Y. Lee, and H. Ischiropoulos Functional consequences of alpha-synuclein tyrosine nitration: diminished binding to lipid vesicles and increased fibril formation J. Biol. Chem. 279 2004 47746 47753 10.1074/jbc.M408906200
135. G. Yamin, C.B. Glaser, V.N. Uversky, and A.L. Fink Certain metals trigger fibrillation of methionine-oxidized alpha-synuclein J. Biol. Chem. 278 2003 27630 27635 10.1074/jbc.M303302200
136. N.B. Cole Metal catalyzed oxidation of alpha-synuclein - a role for oligomerization in pathology? Current 2008 599 606
137. S.R. Paik, Shin. H-j, and Lee. J-h Metal-catalyzed oxidation of α-synuclein in the presence of copper(II) and hydrogen peroxide Arch. Biochem. Biophys. 378 2000 269 277 10.1006/abbi.2000.1822
138. N.B. Cole, D.D. Murphy, J. Lebowitz, L. Di Noto, R.L. Levine, and R.L. Nussbaum Metal-catalyzed oxidation of alpha-synuclein: helping to define the relationship between oligomers, protofibrils, and filaments J. Biol. Chem. 280 2005 9678 9690 10.1074/jbc.M409946200
139. E.J. Jo, J. McLaurin, C.M. Yip, P. St George-Hyslop, and P.E. Fraser Alpha-synuclein membrane interactions and lipid specificity J. Biol. Chem. 275 2000 34328 34334 10.1074/jbc.M004345200
140. H.J. Lee, C. Choi, and S.J. Lee Membrane-bound alpha-synuclein has a high aggregation propensity and the ability to seed the aggregation of the cytosolic form J. Biol. Chem. 277 2002 671 678 10.1074/jbc.M107045200
141. J.A. Wright, X. Wang, and D.R. Brown Unique copper-induced oligomers mediate alpha-synuclein toxicity FASEB J. 23 2009 2384 2393 10.1096/fj.09-130039
142. F. Haque, A.P. Pandey, L.R. Cambrea, J.-C. Rochet, and J.S. Hovis Adsorption of alpha-synuclein on lipid bilayers: modulating the structure and stability of protein assemblies J. Phys. Chem. B 114 2010 4070 4081 10.1021/jp1006704
143. L.A. Munishkina, A.L. Fink, and V.N. Uversky Concerted action of metals and macromolecular crowding on the fibrillation of alpha-synuclein Protein Pept. Lett. 15 2008 1079 1085 10.2174/092986608786071102
144. V.N. Uversky, J. Li, and A.L. Fink Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein - a possible molecular link between Parkinson's disease and heavy metal exposure J. Biol. Chem. 276 2001 44284 44296 10.1074/jbc.M105343200
145. A. Santner, and V.N. Uversky Metalloproteomics and metal toxicology of alpha-synuclein Metallomics 2 2010 378 392 10.1039/b926659c
146. R. Lowe, D.L. Pountney, P.H. Jensen, and W.E.I.P. Gai Calcium(II) selectively induces-synuclein annular oligomers via interaction with the C-terminal domain Protein Sci. 3245-3252 2004 10.1110/ps.04879704.its
147. V.N. Uversky, G. Yamin, P.O. Souillac, J. Goers, C.B. Glaser, and A.L. Fink Methionine oxidation inhibits fibrillation of human alpha-synuclein in vitro FEBS Lett. 517 2002 239 244 10.1016/S0014-5793(02)02638-8
148. C.B. Glaser, G. Yamin, V.N. Uversky, and A.L. Fink Methionine oxidation, alpha-synuclein and Parkinson's disease Biochim. Biophys. Acta, Proteins Proteomics 1703 2005 157 169 10.1016/j.bbapap. 2004.10.008
149. W. Zhou, C. Long, S.H. Reaney, D.A. Di Monte, A.L. Fink, and V.N. Uversky Methionine oxidation stabilizes non-toxic oligomers of alpha-synuclein through strengthening the auto-inhibitory intra-molecular long-range interactions Biochim. Biophys. Acta, Mol. Basis Dis. 1802 2010 322 330 10.1016/j.bbadis.2009. 12.004
150. D.P. Hong, A.L. Fink, and V.N. Uversky Structural characteristics of alpha-synuclein oligomers stabilized by the flavonoid baicalein J. Mol. Biol. 383 2008 214 223 10.1016/j.jmb.2008.08.039
151. A.R. Ladiwala, J. Litt, R.S. Kane, D.S. Aucoin, S.O. Smith, S. Ranjan, J. Davis, W.E. Van Nostrand, and P.M. Tessier Conformational differences between two amyloid beta oligomers of similar size and dissimilar toxicity J. Biol. Chem. 287 2012 24765 24773 10.1074/jbc.M111.329763
152. K.W. Lee, W. Chen, E. Junn, J.Y. Im, H. Grosso, P.K. Sonsalla, X.Y. Feng, N. Ray, J.R. Fernandez, and Y. Chao Enhanced phosphatase activity attenuates alpha-synucleinopathy in a mouse model J. Neurosci. 31 2011 6963 6971 10.1523/Jneurosci.6513-10.2011
153. G.K. Tofaris, A. Razzaq, B. Ghetti, K.S. Lilley, and M.G. Spillantini Ubiquitination of alpha-synuclein in Lewy bodies is a pathological event not associated with impairment of proteasome function J. Biol. Chem. 278 2003 44405 44411 10.1074/jbc.M308041200
154. Y.M. Kim, W.H. Jang, M.M. Quezado, Y. Oh, K.C. Chung, E. Junn, M.M. Mouradian, Y. Man, W. Hee, and K. Chul Proteasome inhibition induces α-synuclein SUMOylation and aggregate formation J. Neurol. Sci. 307 2011 157 161 10.1016/j.jns.2011.04.015
155. K. Beyer Alpha-synuclein structure, posttranslational modification and alternative splicing as aggregation enhancers Acta Neuropathol. 112 2006 237 251 10.1007/s00401-006-0104-6
156. A. Ohrfelt, H. Zetterberg, K. Andersson, R. Persson, D. Secic, G. Brinkmalm, A. Wallin, E. Mulugeta, P.T. Francis, and E. Vanmechelen Identification of novel α-synuclein isoforms in human brain tissue by using an online nano LC-ESI-FTICR-MS method Neurochem. Res. 2011 10.1007/s11064-011-0527-x
157. J.P. Anderson, D.E. Walker, J.M. Goldstein, R. de Laat, K. Banducci, R.J. Caccavello, R. Barbour, J.P. Huang, K. Kling, and M. Lee Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease J. Biol. Chem. 281 2006 29739 29752 10.1074/jbc.M600933200
158. B. Polevoda, J. Norbeck, H. Takakura, A. Blomberg, and F. Sherman Identification and specificities of N-terminal acetyltransferases from Saccharomyces cerevisiae EMBO J. 18 1999 6155 6168 10.1093/emboj/18.21.6155
159. B. Polevoda, and F. Sherman N-terminal acetyltransferases and sequence requirements for N-terminal acetylation of eukaryotic proteins J. Mol. Biol. 325 2003 595 622 10.1016/S0022-2836(02)01269-X
160. K.K. Starheim, D. Gromyko, R. Velde, J.E. Varhaug, and T. Arnesen Composition and biological significance of the human Nalpha-terminal acetyltransferases BMC Proc. 3 Suppl. 6 2009 S3 10.1186/1753-6561-3-S6-S3
161. P. Van Damme, T. Arnesen, and K. Gevaert Protein alpha-N-acetylation studied by N-terminomics FEBS J. 278 2011 3822 3834 10.1111/j.1742-4658.2011. 08230.x
162. A.O. Helbig, S. Gauci, R. Raijmakers, B. van Breukelen, M. Slijper, S. Mohammed, and A.J.R. Heck Profiling of N-acetylated protein termini provides in-depth insights into the N-terminal nature of the proteome Mol. Cell. Proteomics 9 2010 928 939 10.1074/mcp.M900463-MCP200
163. P. Zabrocki, I. Bastiaens, C. Delay, T. Bammens, R. Ghillebert, K. Pellens, C. De Virgilio, F. Van Leuven, and J. Winderickx Phosphorylation, lipid raft interaction and traffic of alpha-synuclein in a yeast model for Parkinson Biochim. Biophys. Acta 1783 2008 1767 1780 10.1016/j.bbamcr.2008.06.010
164. T. Arnesen Towards a functional understanding of protein N-terminal acetylation PLoS Biol. 9 2011 e1001074 10.1371/journal.pbio.1001074
165. G.M. Forte, M.R. Pool, and C.J. Stirling N-terminal acetylation inhibits protein targeting to the endoplasmic reticulum PLoS Biol. 9 2011 e1001073 10.1371/journal.pbio.1001073
166. C.-S. Hwang, A. Shemorry, and A. Varshavsky N-terminal acetylation of cellular proteins creates specific degradation signals Science (New York, NY) 327 2010 973 977 10.1126/science.1183147
167. H. Jornvall Acetylation of protein N-terminal amino groups structural observations on alpha-amino acetylated proteins J. Theor. Biol. 55 1975 1 12
168. A.O. Helbig, S. Rosati, P.W.W.M. Pijnappel, B. van Breukelen, M.H.T.H. Timmers, S. Mohammed, M. Slijper, and A.J.R. Heck Perturbation of the yeast N-acetyltransferase NatB induces elevation of protein phosphorylation levels BMC Genomics 11 2010 685 10.1186/1471-2164-11-685
169. N.J. Greenfield, W.F. Stafford, and S.E. Hitchcock-DeGregori The effect of N-terminal acetylation on the structure of an N-terminal tropomyosin peptide and alpha alpha-tropomyosin Protein Sci. 3 1994 402 410 10.1002/pro.5560030304
170. K. Gast, and C. Fiedler Dynamic and static light scattering of intrinsically disordered proteins Methods Mol. Biol. 896 2012 137 161 10.1007/978-1-4614-3704-8-9
171. O.M.A. El-Agnaf, S.A. Salem, K.E. Paleologou, M.D. Curran, M.J. Gibson, J.A. Court, M.G. Schlossmacher, and D. Allsop Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease FASEB J. 20 2006 419 425 10.1096/fj.03-1449com
172. M. Johnson, A.T. Coulton, Ma Geeves, and D.P. Mulvihill Targeted amino-terminal acetylation of recombinant proteins in E. coli PLoS ONE 5 2010 e15801
173. R. Aurora, and G.D. Rose Helix capping Protein Sci. 7 1998 21 38
174. A. Chakrabartty, A.J. Doig, and R.L. Baldwin Helix capping propensities in peptides parallel those in proteins Proc. Natl. Acad. Sci. USA 90 1993 11332 11336 10.1073/pnas.90.23.11332