Research ArticleOpen AccessGoogle Scholar indexed
Demonstration of three dopamine molecules bound to <i>α</i>-Synuclein: Implication of oligomerization at the initial stage
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
School of Life Science, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
Department of Chemistry, School of Sciences and Engineering, Meisei University, Tokyo, Japan
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
Chemical Analysis Center, Chiba University, Chiba, Japan
Chemical Analysis Center, Chiba University, Chiba, Japan
Department of Chemistry, School of Sciences and Engineering, Meisei University, Tokyo, Japan
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
Department of Chemistry, School of Sciences and Engineering, Meisei University, Tokyo, Japan
- 1 School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
- 2 School of Life Science, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
- 3 Department of Chemistry, School of Sciences and Engineering, Meisei University, Tokyo, Japan
- 4 School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
- 5 School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
- 6 Chemical Analysis Center, Chiba University, Chiba, Japan
- 7 Chemical Analysis Center, Chiba University, Chiba, Japan
- 8 Department of Chemistry, School of Sciences and Engineering, Meisei University, Tokyo, Japan
- 9 School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
- 10 Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
- 11 Department of Chemistry, School of Sciences and Engineering, Meisei University, Tokyo, Japan
Journal of Biophysical Chemistry·Volume 03 (2012)·Pages 149–155·Published 29 May 2012·DOI10.4236/jbpc.2012.32017
Copy link · social · email
Abstract
α -Synuclein is the major component of the filamentous Lewy bodies and Lewy neurites that define neuropathological features and dementia with Lewy bodies. To investigate the role of dopamine (DA) in α -synuclein fibrillation, the structural propensities to form oligomers at the initial stage fibrillation were studied using size exclusion chromatography and various biophysical techniques. Interactions with DA were observed for wild-type α -synuclein and its mutants, A30P, E46K and A53T, using electrospray ionization mass spectrometry (ESI-MS). The results of ESI-MS indicate that an intact α -synuclein, which was not oxidized, had an ability to bind with three molecules of DA at the initial stage. Furthermore, upon binding to DA, α -synuclein oligomerizes to higher molecular weight species. These oligomers are structurally different from amyloid fibrils, as confirmed by thioflavin T and CD analysis.
Keywords<i>α</i>-SynucleinDopamineFibrillationOligomerizationMass Spectrometry
- Uéda, K., Fukushima, H., Masliah, E., Xia, Y., Iwai, A., Yoshimoto, M., Otero, D.A., Kondo, J., Ihara, Y. and Saitoh, T. (1993) Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proceedings of the National Academy of Sciences, 90, 11282-11286. doi:10.1073/pnas.90.23.11282
- Weinreb, P.H., Zhen, W., Poon, A.W., Conway, K.A. and Lansbury, P.T. (1996) NACP, a protein implicated in Alzheimer’s disease and learning, is natively unfolded. Biochemistry, 35, 13709-13715. doi:10.1021/bi961799n
- Davidson, W.S., Jonas, A., Clayton, D.F. and George, J.M. (1998) Stabilization of α-synuclein secondary structure upon binding to synthetic membranes. Journal of Biological Chemistry, 273, 9443-9449. doi:10.1074/jbc.273.16.9443
- George, J.M., Jin, H., Woods, W.S. and Clayton, D.F. (1995) Characterization of a novel protein regulated during the critical period for song learning in the zebra finch. Neuron, 15, 361-372. doi:10.1016/0896-6273(95)90040-3
- Iwai, A., Masliah, E., Yoshimoto, M., Ge, N., Flanagan, L., De Silva, H.A., Kittel, A. and Saitoh, T. (1995) The precursor protein of non-A beta component of Alzheimer’s disease amyloid is a presynaptic protein of the central nervous system. Neuron, 14, 467-475. doi:10.1016/0896-6273(95)90302-X
- Ma, Q.L., Chan, P., Yoshii, M. and Uéda, K. (2003) α-synuclein aggregation and neurodegenerative diseases. Journal of Alzheimer’s Disease, 5, 139-148.
- Yu, S., Li, X., Liu, G., Han, J., Zhang, C., Li, Y., Xu, S., Liu, C., Gao, Y., Yang, H., Uéda, K. and Chan, P. (2007) Extensive nuclear localization of α-synuclein in normal rat brain neurons revealed by a novel monoclonal antibody. Neuroscience, 145, 539-555. doi:10.1016/j.neuroscience.2006.12.028
- 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. and Nussbaum, R.L. (1997) Mutation in the α-synuclein gene identified in families with Parkinson’s disease. Science, 276, 2045-2047. doi:10.1126/science.276.5321.2045
- 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. Nature Genetics, 18, 106-108.
- 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. and De Yebenes, J.G. (2004) The new mutation, E46K, of α-synuclein causes Parkinson and Lewy body dementia. Annals of Neurology, 55, 164-173. doi:10.1002/ana.10795