Alpha-synuclein adopts an alpha-helical conformation in the presence of polyunsaturated fatty acids to hinder micelle formation.
Alpha-synuclein is a small cytosolic protein involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Recent studies suggested a lipid-related function for this brain-enriched protein. Since the brain carries a high level of docosahexaenoic acid (DHA) and since the extent of alpha-synuclein gene expression increases in response to DHA intake, we have investigated the interaction of alpha-synuclein with this essential omega-3 fatty acid. We show that alpha-synuclein allows DHA to be present in a soluble rather than micellar form. Upon interaction with DHA, the normally unstructured alpha-synuclein rapidly adopts an alpha-helical conformation. Prolonged exposure to DHA, however, gradually converts alpha-synuclein into amyloid-like fibrils. These results identify a potential biological function for alpha-synuclein and define an omega-3-linked pathway leading to alpha-synuclein aggregation.
Broersen
Kerensa
K
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
van den Brink
Daan
D
Fraser
Graham
G
Goedert
Michel
M
Davletov
Bazbek
B
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000737:chemistry / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008027:Light; D008823:Micelles; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012542:Scattering, Radiation; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism
D000682:Amyloid; D001095:Arachidonic Acids; D008823:Micelles; D011994:Recombinant Proteins; D051844:alpha-Synuclein; D004281:Docosahexaenoic Acids