N-terminal region of α-synuclein is essential for the fatty acid-induced oligomerization of the molecules

Exposure of alpha-synuclein (alpha S), a major component of Lewy bodies in Parkinson's disease, to polyunsaturated fatty acids (PUFAs) triggers the formation of soluble alpha S oligomers. Here, we demonstrate that PUFA binds recombinant alpha S protein through its N-terminal region ( residues 2-60). In HEK293 cells, alpha S mutants lacking the N-terminal region failed to form oligomers in the presence of PUFA. The PUFA-induced alpha S oligomerization was accelerated by C-terminal truncation or Ser129 phosphorylation of alpha S; however, this effect was abolished by deletion of the N-terminus. The results indicate that the N-terminus of alpha S is essential for the PUFA-induced alpha S oligomerization. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.