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

Exposure of α-synuclein (αS), a major component of Lewy bodies in Parkinson’s disease, to polyunsaturated fatty acids (PUFAs) triggers the formation of soluble αS oligomers. Here, we demonstrate that PUFA binds recombinant αS protein through its N-terminal region (residues 2–60). In HEK293 cells, αS mutants lacking the N-terminal region failed to form oligomers in the presence of PUFA. The PUFA-induced αS oligomerization was accelerated by C-terminal truncation or Ser129 phosphorylation of αS; however, this effect was abolished by deletion of the N-terminus. The results indicate that the N-terminus of αS is essential for the PUFA-induced αS oligomerization.