N-terminal region of alpha-synuclein is essential for the fatty acid-induced oligomerization of the molecules.
Exposure of alpha-synuclein (alphaS), a major component of Lewy bodies in Parkinson's disease, to polyunsaturated fatty acids (PUFAs) triggers the formation of soluble alphaS oligomers. Here, we demonstrate that PUFA binds recombinant alphaS protein through its N-terminal region (residues 2-60). In HEK293 cells, alphaS mutants lacking the N-terminal region failed to form oligomers in the presence of PUFA. The PUFA-induced alphaS oligomerization was accelerated by C-terminal truncation or Ser129 phosphorylation of alphaS; however, this effect was abolished by deletion of the N-terminus. The results indicate that the N-terminus of alphaS is essential for the PUFA-induced alphaS oligomerization.
Karube
Hiroki
H
Department of Neurology, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
Sakamoto
Masahiro
M
Arawaka
Shigeki
S
Hara
Susumu
S
Sato
Hiroyasu
H
Ren
Chang-Hong
CH
Goto
Saori
S
Koyama
Shingo
S
Wada
Manabu
M
Kawanami
Toru
T
Kurita
Keiji
K
Kato
Takeo
T
D000595:Amino Acid Sequence / Q000235:genetics; D002460:Cell Line; D004252:DNA Mutational Analysis; D005231:Fatty Acids, Unsaturated / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D012694:Serine / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
D005231:Fatty Acids, Unsaturated; D011994:Recombinant Proteins; D051844:alpha-Synuclein; D012694:Serine