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End-to-end Structural Restriction of α-Synuclein and Its Influence on Amyloid Fibril Formation

  • Hong, Chul-Suk (School of Chemical and Biological Engineering, Institute of Chemical Processes, College of Engineering, Seoul National University) ;
  • Park, Jae Hyung (School of Chemical and Biological Engineering, Institute of Chemical Processes, College of Engineering, Seoul National University) ;
  • Choe, Young-Jun (School of Chemical and Biological Engineering, Institute of Chemical Processes, College of Engineering, Seoul National University) ;
  • Paik, Seung R. (School of Chemical and Biological Engineering, Institute of Chemical Processes, College of Engineering, Seoul National University)
  • Received : 2014.07.21
  • Accepted : 2014.08.19
  • Published : 2014.12.20

Abstract

Relationship between molecular freedom of amyloidogenic protein and its self-assembly into amyloid fibrils has been evaluated with ${\alpha}$-synuclein, an intrinsically unfolded protein related to Parkinson's disease, by restricting its structural plasticity through an end-to-end disulfide bond formation between two newly introduced cysteine residues on the N- and C-termini. Although the resulting circular form of ${\alpha}$-synuclein exhibited an impaired fibrillation propensity, the restriction did not completely block the protein's interactive core since co-incubation with wild-type ${\alpha}$-synuclein dramatically facilitated the fibrillation by producing distinctive forms of amyloid fibrils. The suppressed fibrillation propensity was instantly restored as the structural restriction was unleashed with ${\beta}$-mercaptoethanol. Conformational flexibility of the accreting amyloidogenic protein to pre-existing seeds has been demonstrated to be critical for fibrillar extension process by exerting structural adjustment to a complementary structure for the assembly.

Keywords

References

  1. Hammer, N. D.; Wang, X.; McGuffie, B. A.; Chapman, M. R. J. Alzheimers Dis. 2008, 13(4), 407-419.
  2. Fowler, D. M.; Koulov, A. V.; Balch, W. E.; Kelly, J. W. Trends Biochem. Sci. 2007, 32(5), 217-224. https://doi.org/10.1016/j.tibs.2007.03.003
  3. Irvine, G. B.; El-Agnaf, O. M.; Shankar, G. M.; Walsh, D. M. Mol. Med. 2008, 14(7-8), 451. https://doi.org/10.1007/s00894-008-0296-x
  4. Ross, C. A.; Poirier, M. A. Nature Med. 2004, 10, S10-S17. https://doi.org/10.1038/nm1066
  5. Chiti, F.; Dobson, C. M. Annu. Rev. Biochem. 2006, 75, 333-366. https://doi.org/10.1146/annurev.biochem.75.101304.123901
  6. Hardy, J.; Selkoe, D. J. Science 2002, 297(5580), 353-356. https://doi.org/10.1126/science.1072994
  7. Chapman, M. R.; Robinson, L. S.; Pinkner, J. S.; Roth, R.; Heuser, J.; Hammar, M.; Normark, S.; Hultgren, S. J. Science 2002, 295(5556), 851-855. https://doi.org/10.1126/science.1067484
  8. Claessen, D.; Rink, R.; de Jong, W.; Siebring, J.; de Vreugd, P.; Boersma, F. H.; Dijkhuizen, L.; Wosten, H. A. Genes Dev. 2003, 17(14), 1714-1726. https://doi.org/10.1101/gad.264303
  9. Nelson, R.; Sawaya, M. R.; Balbirnie, M.; Madsen, A. O.; Riekel, C.; Grothe, R.; Eisenberg, D. Nature 2005, 435(7043), 773-778. https://doi.org/10.1038/nature03680
  10. Corrigan, A. M.; Muller, C.; Krebs, M. R. J. Am. Chem. Soc. 2006, 128(46), 14740-14741. https://doi.org/10.1021/ja064455l
  11. Bhak, G.; Lee, S.; Park, J. W.; Cho, S.; Paik, S. R. Biomaterials 2010, 31(23), 5986-5995. https://doi.org/10.1016/j.biomaterials.2010.03.080
  12. Knowles, T. P.; Fitzpatrick, A. W.; Meehan, S.; Mott, H. R.; Vendruscolo, M.; Dobson, C. M.; Welland, M. E. Science 2007, 318(5858), 1900-1903. https://doi.org/10.1126/science.1150057
  13. Smith, J. F.; Knowles, T. P.; Dobson, C. M.; MacPhee, C. E.; Welland, M. E. Proc. Natl. Acad. Sci. USA 2006, 103(43), 15806-15811. https://doi.org/10.1073/pnas.0604035103
  14. Puchtler, H.; Sweat, F.; Levine, M. J. Histochem. Cytochem. 1962, 10(3), 355-364. https://doi.org/10.1177/10.3.355
  15. Ridgley, D. M.; Barone, J. R. ACS nano 2013, 7(2), 1006-1015. https://doi.org/10.1021/nn303489a
  16. Lee, D.; Choe, Y. J.; Choi, Y. S.; Bhak, G.; Lee, J.; Paik, S. R. Angew. Chem. Int. Ed. 2011, 50(6), 1332-1337. https://doi.org/10.1002/anie.201004301
  17. Knowles, T. P.; Oppenheim, T. W.; Buell, A. K.; Chirgadze, D. Y.; Welland, M. E. Nat. Nanotechnol. 2010, 5(3), 204-207. https://doi.org/10.1038/nnano.2010.26
  18. Chun, J.; Bhak, G.; Lee, S. G.; Lee, J. H.; Lee, D.; Char, K.; Paik, S. R. Biomacromolecules 2012, 13(9), 2731-2738. https://doi.org/10.1021/bm300692k
  19. Choi, Y. S.; Kim, J.; Bhak, G.; Lee, D.; Paik, S. R. Angew. Chem. Int. Ed. 2011, 123(27), 6194-6198. https://doi.org/10.1002/ange.201006859
  20. Li, C.; Adamcik, J.; Mezzenga, R. Nat. Nanotechnol. 2012, 7(7), 421-427. https://doi.org/10.1038/nnano.2012.62
  21. Scheibel, T.; Parthasarathy, R.; Sawicki, G.; Lin, X. M.; Jaeger, H.; Lindquist, S. L. Proc. Natl. Acad. Sci. USA 2003, 100(8), 4527-4532. https://doi.org/10.1073/pnas.0431081100
  22. De Simone, A.; Kitchen, C.; Kwan, A. H.; Sunde, M.; Dobson, C. M.; Frenkel, D. Proc. Natl. Acad. Sci. USA 2012, 109(18), 6951-6956. https://doi.org/10.1073/pnas.1118048109
  23. Uversky, V. N.; Fink, A. L. Biochim. Biophys. Acta 2004, 1698(2), 131-153. https://doi.org/10.1016/j.bbapap.2003.12.008
  24. Ueda, K.; Fukushima, H.; Masliah, E.; Xia, Y.; Iwai, A.; Yoshimoto, M.; Otero, D. A.; Kondo, J.; Ihara, Y.; Saitoh, T. Proc. Natl. Acad. Sci. USA 1993, 90(23), 11282-11286. https://doi.org/10.1073/pnas.90.23.11282
  25. Arima, K.; Ueda, K.; Sunohara, N.; Hirai, S.; Izumiyama, Y.; Tonozuka-Uehara, H.; Kawai, M. Brain Res. 1998, 808(1), 93-100. https://doi.org/10.1016/S0006-8993(98)00734-3
  26. Arima, K.; Ueda, K.; Sunohara, N.; Arakawa, K.; Hirai, S.; Nakamura, M.; Tonozuka-Uehara, H.; Kawai, M. Acta Neuropathol. 1998, 96(5), 439-444. https://doi.org/10.1007/s004010050917
  27. Rasia, R. M.; Bertoncini, C. W.; Marsh, D.; Hoyer, W.; Cherny, D.; Zweckstetter, M.; Griesinger, C.; Jovin, T. M.; Fernandez, C. O. Proc. Natl. Acad. Sci. USA 2005, 102(12), 4294-4299. https://doi.org/10.1073/pnas.0407881102
  28. Davidson, W. S.; Jonas, A.; Clayton, D. F.; George, J. M. J. Biol. Chem. 1998, 273(16), 9443-9449. https://doi.org/10.1074/jbc.273.16.9443
  29. Giasson, B. I.; Murray, I. V.; Trojanowski, J. Q.; Lee, V. M. Y. J. Biol. Chem. 2001, 276(4), 2380-2386. https://doi.org/10.1074/jbc.M008919200
  30. Heise, H.; Hoyer, W.; Becker, S.; Andronesi, O. C.; Riedel, D.; Baldus, M. Proc. Natl. Acad. Sci. USA 2005, 102(44), 15871-15876. https://doi.org/10.1073/pnas.0506109102
  31. Dedmon, M. M.; Lindorff-Larsen, K.; Christodoulou, J.; Vendruscolo, M.; Dobson, C. M. J. Am. Chem. Soc. 2005, 127(2), 476-477. https://doi.org/10.1021/ja044834j
  32. Bertoncini, C. W.; Jung, Y. S.; Fernandez, C. O.; Hoyer, W.; Griesinger, C.; Jovin, T. M.; Zweckstetter, M. Proc. Natl. Acad. Sci. USA 2005, 102(5), 1430-1435. https://doi.org/10.1073/pnas.0407146102
  33. Ullman, O.; Fisher, C. K.; Stultz, C. M. J. Am. Chem. Soc. 2011, 133(48), 19536-19546. https://doi.org/10.1021/ja208657z
  34. Kosower, N. S.; Kosower, E. M.; Wertheim, B.; Correa, W. S. Biochem. Biophys. Res. Commun. 1969, 37(4), 593-596. https://doi.org/10.1016/0006-291X(69)90850-X