Demonstration of three dopamine molecules bound to α-Synuclein: Implication of oligomerization at the initial stage

Sakurako Shimotakahara, Yuuki Shiroyama, Takashi Fujimoto, Mai Akai, Takaya Onoue, Hiroko Seki, Sayaka Kado, Tomoya Machinami, Yoichi Shibusawa, Kenji Uéda, Mitsuru Tashiro

Chemical Analysis Center, Chiba University, Chiba, Japan.
Department of Chemistry, School of Sciences and Engineering, Meisei University, Tokyo, Japan.
Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
School of Life Science, Tokyo University of Pharmacy and Life Science, Tokyo, Japan.
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan.

DOI: 10.4236/jbpc.2012.32017                

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

α-Synuclein; Dopamine; Fibrillation; Oligomerization; Mass Spectrometry

Conflicts of Interest

The authors declare no conflicts of interest.

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