Structures and free energy landscapes of the wild-type and A30P mutant-type α-synuclein proteins with dynamics

ACS Chemical Neuroscience

Volumn 4, Issue 3, 2013, Pages 486-497

  Wise Scira, Olivia ^a   Aloglu, Ahmet Kemal ^a   Dunn, Aquila ^a   Sakallioglu, Isin Tuna ^b   Coskuner, Orkid ^a  

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

^b BILKENT UNIVERSITY   (Turkey)

Author keywords

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

Indexed keywords

ALPHA SYNUCLEIN;

A30 MUTANT TYPE; AQUEOUS SOLUTION; ARTICLE; BETA SHEET; ENERGY TRANSFER; GENE MUTATION; MOLECULAR DYNAMICS; MOLECULAR LIBRARY; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN INTERACTION; PROTEIN STRUCTURE; THERMODYNAMICS; WILD TYPE;

ALANINE; ALPHA-SYNUCLEIN; ENERGY METABOLISM; HUMANS; MOLECULAR DYNAMICS SIMULATION; MUTANT PROTEINS; MUTATION, MISSENSE; PROLINE; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY;

EID: 84875523636     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/cn300198q     Document Type: Article

References (60)

1. 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
2. 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
3. Kruger, R., Muller, T., and Riess, O. (2000) Involvement of alpha-synuclein in Parkinson's disease and other neurodegenerative disorders J. Neural Transm. 107, 31-40
4. Maroteaux, L., Campanelli, J. T., and Scheller, R. H. (1988) Synuclein-A Neuron-specific protein localized to the nucleus and presynaptic nerve-terminal J. Neurosci. 8, 2804-2815
5. Polymeropoulos, M. H., Higgins, J. J., Golbe, L. I., Johnson, W. G., Ide, S. E., DiIorio, G., Sanges, G., Stenroos, E. S., Pho, L. T., Schaffer, A. A., Lazzarini, A. M., Nussbaum, R. L., and Duvoisin, R. C. (1996) Mapping of a gene for Parkinson's disease to chromosome 4q21-q23 Science 274, 1197-1199
6. Goedert, M. (2001) Parkinson's disease and other alpha-synucleinopathies Clin. Chem. Lab. Med. 39, 308-312
7. Singleton, A. B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., Nussbaum, R., Lincoln, S., Crawley, A., Hanson, M., Maraganore, D., Adler, C., Cookson, M. R., Muenter, M., Baptista, M., Miller, D., Blancato, J., Hardy, J., and Gwinn-Hardy, K. (2003) alpha-synuclein locus triplication causes Parkinson's disease Science 302, 841-841
8. 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
9. 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
10. 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
11. 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
12. 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
13. 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
14. 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
15. 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 Na. Med. 4, 1318-1320
16. El-Agnaf, O. M. A., Jakes, R., Curran, M. D., and Wallace, A. (1998) Effects of the mutations Ala(30) to Pro and Ala(53) to Thr on the physical and morphological properties of alpha-synuclein protein implicated in Parkinson's disease FEBS Lett. 440, 67-70
17. 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
18. 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
19. Cho, M. K., Kim, H. Y., Fernandez, C. O., Becker, S., and Zweckstetter, M. (2011) Conserved core of amyloid fibrils of wild type and A30P mutant alpha-synuclein Protein Sci. 20, 387-395
20. 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
21. 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
22. 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
23. 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
24. Ono, K., Ikeda, T., Takasaki, J., and Yamada, M. (2011) Familial Parkinson disease mutations influence alpha-synuclein assembly Neurobiol. Dis. 43, 715-724
25. 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
26. 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
27. 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
28. Bertoncini, C. W., Fernandez, C. O., Griesinger, C., Jovin, T. M., and Zweckstetter, M. (2005) Familial mutants of alpha-synuclein with increased neurotoxicity have a destabilized conformation J. Biol. Chem. 280, 30649-30652
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. 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
31. Ferreon, A. C. M., Moran, C. R., Ferreon, J. C., and Deniz, A. A. (2010) Alteration of the alpha-Synuclein Folding Landscape by a Mutation Related to Parkinson's Disease Angew. Chem., Int. Ed. 49, 3469-3472
32. 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
33. 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
34. 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
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, 123-133
36. 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
37. 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.
38. 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
39. Coskuner, O., Wise-Scira, O., Perry, G., and Kitahara, T. (2012) The Structures 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. DOI: 10/1021/cn300149j.
40. 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., in press.
41. Barrow, C. J. and Zagorski, M. G. (1991) Solution Structures of Beta Peptide and Its Constituent Fragments-Relation to Amyloid Deposition Science 253, 179-182
42. Kessler, J. C., Rochet, J. C., and Lansbury, P. T. (2003) The N-terminal repeat domain of alpha-synuclein inhibits beta-sheet and amyloid fibril formation Biochemistry 42, 672-678
43. Kim, Y. S., Lim, D., Kim, J. Y., Kang, S. J., Kim, Y.-H., and Im, H. (2009) beta-Sheet-breaking peptides inhibit the fibrillation of human alpha-synuclein Biochem. Biophys. Res. Commun. 387, 682-687
44. 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
45. Giasson, B. I., Murray, I. V. J., Trojanowski, J. Q., and Lee, V. M. Y. (2001) A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly J. Biol. Chem. 276, 2380-2386
46. Lee, J. C., Langen, R., Hummel, P. A., Gray, H. B., and Winkler, J. R. (2004) alpha-synuclein structures from fluorescence energy-transfer kinetics: Implications for the role of the protein in Parkinson's disease Proc. Natl. Acad. Sci. U.S.A. 101, 16466-16471
47. Sugita, Y. and Okamoto, Y. (1999) Replica-exchange molecular dynamics method for protein folding Chem. Phys. Lett. 314, 141-151
48. Zhang, W., Wu, C., and Duan, Y. (2005) Convergence of replica exchange molecular dynamics J. Chem. Phys. 123, 154105
49. 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
50. 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.
51. 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
52. van der Spoel, D. and Patriksson, A. (2008) A temperature predictor for parallel tempering simulations Phys. Chem. Chem. Phys. 10, 2073-2077
53. Allen, M. P. and Tildesley, D. J. (1999) Computer simulation of liquids, Clarendon Press: Oxford.
54. Frenkel, D. and Smit, B. (2002) Understanding molecular simulation: from algorithms to applications, Vol. 1, Academic Press: San Diego, CA.
55. Kabsch, W. and Sander, C. (1983) Dictionary of Protein Secondary Structure-Pattern-Recognition of Hydrogen-Bonded and Geometrical Features Biopolymers 22, 2577-2637
56. Lee, M. R., Duan, Y., and Kollman, P. A. (2000) Use of MM-PB/SA in estimating the free energies of proteins: Application to native, intermediates, and unfolded villin headpiece Proteins: Struct., Funct., Genet. 39, 309-316
57. Kollman, P. A., Massova, I., Reyes, C., Kuhn, B., Huo, S. H., Chong, L., Lee, M., Lee, T., Duan, Y., Wang, W., Donini, O., Cieplak, P., Srinivasan, J., Case, D. A., and Cheatham, T. E. (2000) Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models Acc. Chem. Res. 33, 889-897
58. Case, D. A. (1994) Normal-Mode Analysis of Protein Dynamics Curr. Opin. Struct. Biol. 4, 285-290
59. Schlitter, J. (1993) Estimation of Absolute and Relative Entropies of Macromolecules Using the Covariance-Matrix Chem. Phys. Lett. 215, 617-621
60. Kumar, S., Sarkar, A., and Sundar, D. (2009) Controlling the aggregation propensity in A53T mutant of alpha-synuclein causing Parkinson's Disease Biochem. Biophys. Res. Comm. 387, 305-309