Structures and free energy landscapes of the A53T mutant-type α-synuclein protein and impact of A53T mutation on the structures of the wild-type α-synuclein protein with dynamics

ACS Chemical Neuroscience

Volumn 4, Issue 7, 2013, Pages 1101-1113

  Coskuner, Orkid ^a   Wise Scira, Olivia ^a  

^a UNIVERSITY OF TEXAS AT SAN ANTONIO   (United States)

Author keywords

Synuclein; free energy landscape; genetic missense mutation; molecular dynamics simulations

Indexed keywords

ALPHA SYNUCLEIN;

A53T GENE; AQUEOUS SOLUTION; ARTICLE; ATOM; BETA SHEET; ENERGY; GENE; MISSENSE MUTATION; MOLECULAR DYNAMICS; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN CONFORMATION; PROTEIN INTERACTION; PROTEIN STRUCTURE; THERMODYNAMICS;

ALCOHOL OXIDOREDUCTASES; ALPHA-SYNUCLEIN; DNA-BINDING PROTEINS; ENTROPY; HUMANS; MOLECULAR DYNAMICS SIMULATION; MUTANT PROTEINS; MUTATION, MISSENSE; PARKINSON DISEASE; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY;

EID: 84880394668     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/cn400041j     Document Type: Article

References (75)

1. Goedert, M. (2001) Alpha-synuclein and neurodegenerative diseases Nat. Rev. Neurosci. 2, 492-501
2. Braak, H., Del Tredici, K., Rub, U., de Vos, R. A. I., Steur, E., and Braak, E. (2003) Staging of brain pathology related to sporadic Parkinson's disease Neurobiol. Aging 24, 197-211
3. Spillantini, M. G., Schmidt, M. L., Lee, V. M. Y., Trojanowski, J. Q., Jakes, R., and Goedert, M. (1997) Alpha-synuclein in Lewy bodies Nature 388, 839-840
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., DiIorio, G., Golbe, L. I., and Nussbaum, R. L. (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson's disease Science 276, 2045-2047
5. 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., Tortosa, E. G., del Ser, T., Munoz, D. G., and de Yebenes, J. G. (2004) The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia Ann. Neurol. 55, 164-173
6. Kruger, R., Kuhn, W., Muller, T., Woitalla, D., Graeber, M., Kosel, S., Przuntek, H., Epplen, J. T., Schols, L., and Riess, O. (1998) Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease Nat. Genet. 18, 106-108
7. Winner, B., Jappelli, R., Maji, S. K., Desplats, P. A., Boyer, L., Aigner, S., Hetzer, C., Loher, T., Vilar, M., Campionic, S., Tzitzilonis, C., Soragni, A., Jessberger, S., Mira, H., Consiglio, A., Pham, E., Masliah, E., Gage, F. H., and Riek, R. (2011) In vivo demonstration that alpha-synuclein oligomers are toxic Proc. Natl. Acad. Sci. U.S.A. 108, 4194-4199
8. Outeiro, T. F., Putcha, P., Tetzlaff, J. E., Spoelgen, R., Koker, M., Carvalho, F., Hyman, B. T., and McLean, P. J. (2008) Formation of Toxic Oligomeric α-Synuclein Species in Living Cells Plos One 3 e1867
9. Li, J., Uversky, V. N., and Fink, A. L. (2001) Effect of familial Parkinson's disease point mutations A30P and A53T on the structural properties, aggregation, and fibrillation of human alpha-synuclein Biochemistry 40, 11604-11613
10. Li, J., Uversky, V. N., and Fink, A. L. (2002) Conformational behavior of human alpha-synuclein is modulated by familial Parkinson's disease point mutations A30P and A53T Neurotoxicology 23, 553-567
11. Choong, C. J. and Say, Y. H. (2011) Neuroprotection of alpha-synuclein under acute and chronic rotenone and maneb treatment is abolished by its familial Parkinson's disease mutations A30P, A53T and E46K Neurotoxicology 32, 857-863
12. Wersinger, C. and Sidhu, A. (2003) Differential cytotoxicity of dopamine and H2O2 in a human neuroblastoma divided cell line transfected with alpha-synuclein and its familial Parkinson's disease-linked mutants Neurosci. Lett. 342, 124-128
13. Moussa, C. E. H., Wersinger, C., Tomita, Y., and Sidhu, A. (2004) Differential cytotoxicity of human wild type and mutant alpha-synuclein in human neuroblastoma SH-SY5Y cells in the presence of dopamine Biochemistry 43, 5539-5550
14. Bussell, R. and Eliezer, D. (2004) Effects of Parkinson's disease-linked mutations on the structure of lipid-associated alpha-synuclein Biochemistry 43, 4810-4818
15. Choi, W., Zibaee, S., Jakes, R., Serpell, L. C., Davletov, B., Crowther, R. A., and Goedert, M. (2004) Mutation E46K increases phospholipid binding and assembly into filaments of human alpha-synuclein FEBS Lett. 576, 363-368
16. Jensen, P. H., Nielsen, M. S., Jakes, R., Dotti, G., and Goedert, M. (1998) Binding of alpha-synuclein to brain vesicles is abolished by familial Parkinson's disease mutation J. Biol. Chem. 273, 26292-26294
17. Jo, E. J., Fuller, N., Rand, R. P., St George-Hyslop, P., and Fraser, P. E. (2002) Defective membrane interactions of familial Parkinson's disease mutant A30P alpha-synuclein J. Mol. Biol. 315, 799-807
18. Perrin, R. J., Woods, W. S., Clayton, D. F., and George, J. M. (2000) Interaction of human alpha-synuclein and Parkinson's disease variants with phospholipids-Structural analysis using site-directed mutagenesis J. Biol. Chem. 275, 34393-34398
19. Ding, T. T., Lee, S. J., Rochet, J. C., and Lansbury, P. T. (2002) Annular alpha-synuclein protofibrils are produced when spherical protofibrils are incubated in solution or bound to brain-derived membranes Biochemistry 41, 10209-10217
20. Volles, M. J., Lee, S. J., Rochet, J. C., Shtilerman, M. D., Ding, T. T., Kessler, J. C., and Lansbury, P. T. (2001) Vesicle permeabilization by protofibrillar alpha-synuclein: Implications for the pathogenesis and treatment of Parkinson's disease Biochemistry 40, 7812-7819
21. Conway, K. A., Harper, J. D., and Lansbury, P. T. (1998) Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease Nat. Med. 4, 1318-1320
22. Giasson, B. I., Uryu, K., Trojanowski, J. Q., and Lee, V. M. Y. (1999) Mutant and wild type human alpha-synucleins assemble into elongated filaments with distinct morphologies in vitro J. Biol. Chem. 274, 7619-7622
23. Serpell, L. C., Berriman, J., Jakes, R., Goedert, M., and Crowther, R. A. (2000) Fiber diffraction of synthetic alpha-synuclein filaments shows amyloid-like cross-beta conformation Proc. Natl. Acad. Sci. U. S. A. 97, 4897-4902
24. Kamiyoshihara, T., Kojima, M., Ueda, K., Tashiro, M., and Shimotakahara, S. (2007) Observation of multiple intermediates in alpha-synuclein fibril formation by singular value decomposition analysis Biochem. Biophys. Res. Commun. 355, 398-403
25. Lashuel, H. A., Petre, B. M., Wall, J., Simon, M., Nowak, R. J., Walz, T., and Lansbury, P. T. (2002) alpha-synuclein, especially the Parkinson's disease-associated mutants, forms pore-like annular and tubular protofibrils J. Mol. Biol. 322, 1089-1102
26. Conway, K. A., Lee, S. J., Rochet, J. C., Ding, T. T., Williamson, R. E., and Lansbury, P. T. (2000) 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. U. S. A. 97, 571-576
27. Narhi, L., Wood, S. J., Steavenson, S., Jiang, Y. J., Wu, G. M., Anafi, D., Kaufman, S. A., Martin, F., Sitney, K., Denis, P., Louis, J. C., Wypych, J., Biere, A. L., and Citron, M. (1999) Both familial Parkinson's disease mutations accelerate alpha-synuclein aggregation J. Biol. Chem. 274, 9843-9846
28. Ono, K., Ikeda, T., Takasaki, J., and Yamada, M. (2011) Familial Parkinson disease mutations influence alpha-synuclein assembly Neurobiol. Dis. 43, 715-724
29. Bussell, R. and Eliezer, D. (2001) Residual structure and dynamics in Parkinson's disease-associated mutants of alpha-synuclein J. Biol. Chem. 276, 45996-46003
30. Heise, H., Celej, M. S., Becker, S., Riede, D., Pelah, A., Kumar, A., Jovin, T. M., and Baldus, M. (2008) Solid-state NMR reveals structural differences between fibrils of wild-type and disease-related A53T mutant alpha-synuclein J. Mol. Biol. 380, 444-450
31. Brucale, M., Sandal, M., Di Maio, S., Rampioni, A., Tessari, I., Tosatto, L., Bisaglia, M., Bubacco, L., and Samori, B. (2009) Pathogenic mutations shift the equilibria of alpha-synuclein single molecules towards structured conformers ChemBioChem 10, 176-183
32. Bertoncini, C. W., Jung, Y. S., Fernandez, C. O., Hoyer, W., Griesinger, C., Jovin, T. M., and Zweckstetter, M. (2005) Release of long-range tertiary interactions potentiates aggregation of natively unstructured alpha-synuclein Proc. Natl. Acad. Sci. U. S. A. 102, 1430-1435
33. Kumar, S., Sarkar, A., and Sundar, D. (2009) Controlling aggregation propensity in A53T mutant of alpha-synuclein causing Parkinson's disease Biochem. Biophys. Res. Commun. 387, 305-309
34. Perlmutter, J. D., Braun, A. R., and Sachs, J. N. (2009) Curvature dynamics of alpha-synuclein familial parkinson disease mutants molecular simulations of the micelle- and bilayer-bound forms J. Biol. Chem. 284, 7177-7189
35. Balesh, D., Ramjan, Z., and Floriano, W. B. (2011) Unfolded annealing molecular dynamics conformers for wild-type and disease-associated variants of alpha-synuclein show no propensity for beta-sheet formation J. Biophys. Chem. 2, 124-134
36. Losasso, V., Pietropaolo, A., Zannoni, C., Gustincich, S., and Carloni, P. (2011) Structural role of compensatory amino acid replacements in the alpha-synuclein protein Biochemistry 50, 6994-7001
37. Jonsson, S. A., Mohanty, S., and Irback, A. (2012) Distinct phases of free alpha-synuclein-A Monte Carlo study Proteins 80, 2169-2177
38. Clayton, D. F. and George, J. M. (1998) The synucleins: A family of proteins involved in synaptic function, plasticity, neurodegeneration and disease Trends Neurosci. 21, 249-254
39. Davidson, W. S., Jonas, A., Clayton, D. F., and George, J. M. (1998) Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes J. Biol. Chem. 273, 9443-9449
40. Jo, E. J., McLaurin, J., Yip, C. M., St George-Hyslop, P., and Fraser, P. E. (2000) Alpha-synuclein membrane interactions and lipid specificity J. Biol. Chem. 275, 34328-34334
41. Conway, K. A., Harper, J. D., and Lansbury, P. T. (2000) Fibrils formed in vitro from alpha-synuclein and two mutant forms linked to Parkinson's disease are typical amyloi Biochemistry 39, 2552-2563
42. Coskuner, O., Wise-Scira, O., Perry, G., and Kitahara, T. (2013) The structure of the E22Δ mutant-type amyloid-β alloforms and the impact of E22Δ mutation on the structures of the wild-type amyloid-β alloforms ACS Chem. Neurosci. 4, 310-320
43. Uversky, V. N. (2007) Neuropathology, biochemistry, and biophysics of alpha-synuclein aggregation J. Neurochem. 103, 17-37
44. Wise-Scira, O., Dunn, A., Aloglu, A. K., Sakallioglu, I. T., and Coskuner, O. (2013) Structures of the E46K mutant-type α-synuclein protein and impact of E46K mutation on the structures of the wild-type α-synuclein protein ACS Chem. Neurosci. 4, 498-508
45. Hazy, E., Bokor, M., Kalmar, L., Gelencser, A., Kamasa, P., Han, K. H., Tompa, K., and Tompa, P. (2011) Distinct hydration properties of wild-type and familial point mutant A53T of alpha-synuclein associated with Parkinson's disease Biophys. J. 101, 2260-2266
46. Wise-Scira, O., Aloglu, A. K., Dunn, A., Sakallioglu, I. T., and Coskuner, O. (2013) Structures and free energy landscapes of the wild-type and A30P mutant-type α-synuclein proteins with dynamics ACS Chem. Neurosci. 4, 486-497
47. Wise-Scira, O., Xu, L., Kitahara, T., Perry, G., and Coskuner, O. (2011) Amyloid-beta peptide structure in aqueous solution varies with fragment size J. Chem. Phys. 135 205101
48. Wise-Scira, O., Xu, L., Perry, G., and Coskuner, O. (2012) Structures and free energy landscapes of aqueous zinc(II)-bound amyloid-beta(1-40) and zinc(II)-bound amyloid-beta(1-42) with dynamics J. Biol. Inorg. Chem. 17, 927-938
49. Sugita, Y. and Okamoto, Y. (1999) Replica-exchange molecular dynamics method for protein folding Chem. Phys. Lett. 314, 141-151
50. Zhang, W., Wu, C., and Duan, Y. (2005) Convergence of replica exchange molecular dynamics J. Chem. Phys. 123 154105
51. Case, D., Darden, T., Cheatham, T., Simmerling, C., Wang, J., Duke, R., Luo, R., Walker, R., Zhang, W., and Merz, K. (2010) AMBER 11, University of California, San Francisco.
52. Hornak, V., Abel, R., Okur, A., Strockbine, B., Roitberg, A., and Simmerling, C. (2006) Comparison of multiple amber force fields and development of improved protein backbone parameters Proteins 65, 712-725
53. Case, D. A., Onufriev, A., and Bashford, D. (2004) Exploring protein native states and large-scale conformational changes with a modified generalized born model Proteins 55, 383-394
54. Windisch, M., Wolf, H., Hutter-Paier, B., and Wronski, R. (2008) The role of alpha-synuclein in neurodegenerative diseases: A potential target for new treatment strategies? Neurodegener. Dis. 5, 218-221
55. van der Spoel, D. and Patriksson, A. (2008) A temperature predictor for parallel tempering simulations Phys. Chem. Chem. Phys. 10, 2073-2077
56. Allen, M. P. and Tildesley, D. J. (1999) Computer Simulation of Liquids; Clarendon Press, Oxford, U.K.
57. Frenkel, D. and Smit, B. (2002) Understanding Molecular Simulation: From Algorithms to Applications, Vol. 1, Academic Press, San Diego, CA.
58. Ryckaert, J. P., Ciccotti, G., and Berendsen, H. J. C. (1977) Numerical integration of the Cartesian equations of motion of a system with constraints: Molecular dynamics of n -alkanes J. Comput. Phys. 23, 327-341
59. Chatterjee, P. and Sengupta, N. (2012) Effect of the A30P mutation on the structural dynamics of micelle-bound alpha Synuclein released in water: a molecular dynamics study Eur. Biophys. J. Biophys. Lett. 41, 483-489
60. Baumketner, A. and Shea, J. E. (2006) Folding landscapes of the Alzheimer amyloid-beta(12-28) peptide J. Mol. Biol. 362, 567-579
61. Xu, Y. C., Shen, J. J., Luo, X. M., Zhu, W. L., Chen, K. X., Ma, J. P., and Jiang, H. L. (2005) Conformational transition of amyloid beta-peptide Proc. Natl. Acad. Sci. U. S. A. 102, 5403-5407
62. Lee, C. and Ham, S. (2011) Characterizing amyloid-beta protein misfolding from molecular dynamics simulations with explicit water J. Comput. Chem. 32, 349-355
63. Brovchenko, I., Burri, R. R., Krukau, A., Oleinikova, A., and Winter, R. (2008) Intrinsic thermal expansivity and hydrational properties of amyloid peptide A beta(42) in liquid water J. Chem. Phys. 129 195101
64. Raffa, D. F. and Rauk, A. (2007) Molecular dynamics study of the beta amyloid peptide of Alzheimer's disease and its divalent copper complexes J. Phys. Chem. B 111, 3789-3799
65. Triguero, L., Singh, R., and Prabhakar, R. (2008) Comparative molecular dynamics studies of wild-type and oxidized forms of full-length Alzheimer amyloid beta-peptides A beta(1-40) and A beta(1-42) J. Phys. Chem. B 112, 7123-7131
66. Cruz, L., Urbanc, B., Borreguero, J. M., Lazo, N. D., Teplow, D. B., and Stanley, H. E. (2005) Solvent and mutation effects on the nucleation of amyloid beta-protein folding Proc. Natl. Acad. Sci. U. S. A. 102, 18258-18263
67. Luttmann, E. and Fels, G. (2006) All-atom molecular dynamics studies of the full-length beta-amyloid peptides Chem. Phys. 323, 138-147
68. Sgourakis, N. G., Yan, Y. L., McCallum, S. A., Wang, C. Y., and Garcia, A. E. (2007) The Alzheimer's peptides A beta 40 and 42 adopt distinct conformations in water: A combined MD/NMR study J. Mol. Biol. 368, 1448-1457
69. Andersen, H. C. (1983) RATTLE: A "Velocity" version of the SHAKE algorithm for molecular dynamics calculations J. Comput. Phys. 52, 24-34
70. Fawver, J. N., Duong, K. T., Wise-Scira, O., Schall, H. E., Coskuner, O., Zhu, X., Colom, L. V., and Murray, I. V. J. (2012) Probing and trapping a sensitive conformation: Amyloid-β fibrils, oligomers, and dimers J. Alzheimer's Dis. 32, 197-215
71. Kabsch, W. and Sander, C. (1983) Dictionary of protein secondary structure-pattern-recognition of hydrogen-bonded and geometrical features Biopolymers 22, 2577-2637
72. Case, D. A. (1994) Normal-mode analysis of protein dynamics Curr. Opin. Struct. Biol. 4, 285-290
73. Schlitter, J. (1993) Estimation of absolute and relative entropies of macromolecules using the covariance-matrix Chem. Phys. Lett. 215, 617-621
74. Coskuner, O. and Deiters, U. K. (2006) Hydrophobic interactions by Monte Carlo simulations Z. Phys. Chem. 220, 349-369
75. Coskuner, O. and Deiters, U. K. (2007) Hydrophobic interactions of xenon by Monte Carlo simulations Z. Phys. Chem. 221, 785-799-799