TY - JOUR
T1 - The structure of dopamine induced alpha-synuclein oligomers
AU - Rekas, Agata
AU - Knott, Robert
AU - Sokolova, Anna
AU - Barnham, Kevin
AU - Perez, Keyla
AU - Masters, Colin
AU - Drew, Simon
AU - Cappai, Roberto
AU - Curtain, Cyril
PY - 2010
Y1 - 2010
N2 - Inclusions of aggregated I?-synuclein (I?-syn) in dopaminergic neurons are a characteristic histological marker of Parkinson s disease (PD). In vitro, I?-syn in the presence of dopamine (DA) at physiological pH forms SDS-resistant non-amyloidogenic oligomers. We used a combination of biophysical techniques, including sedimentation velocity analysis, small angle X-ray scattering (SAXS) and circular dichroism spectroscopy to study the characteristics of I?-syn oligomers formed in the presence of DA. Our SAXS data show that the trimers formed by the action of DA on I?-syn consist of overlapping worm-like monomers, with no end-to-end associations. This lack of structure contrasts with the well-established, extensive I?-sheet structure of the amyloid fibril form of the protein and its pre-fibrillar oligomers. We propose on the basis of these and earlier data that oxidation of the four methionine residues at the C- and N-terminal ends of I?-syn molecules prevents their end-to-end association and stabilises oligomers formed by cross linking with DA-quinone/DA-melanin, which are formed as a result of the redox process, thus inhibiting formation of the I?-sheet structure found in other pre-fibrillar forms of I?-syn
AB - Inclusions of aggregated I?-synuclein (I?-syn) in dopaminergic neurons are a characteristic histological marker of Parkinson s disease (PD). In vitro, I?-syn in the presence of dopamine (DA) at physiological pH forms SDS-resistant non-amyloidogenic oligomers. We used a combination of biophysical techniques, including sedimentation velocity analysis, small angle X-ray scattering (SAXS) and circular dichroism spectroscopy to study the characteristics of I?-syn oligomers formed in the presence of DA. Our SAXS data show that the trimers formed by the action of DA on I?-syn consist of overlapping worm-like monomers, with no end-to-end associations. This lack of structure contrasts with the well-established, extensive I?-sheet structure of the amyloid fibril form of the protein and its pre-fibrillar oligomers. We propose on the basis of these and earlier data that oxidation of the four methionine residues at the C- and N-terminal ends of I?-syn molecules prevents their end-to-end association and stabilises oligomers formed by cross linking with DA-quinone/DA-melanin, which are formed as a result of the redox process, thus inhibiting formation of the I?-sheet structure found in other pre-fibrillar forms of I?-syn
UR - http://www.springerlink.com.ezproxy.lib.monash.edu.au/content/6j10166u232110u3/fulltext.pdf
U2 - 10.1007/s00249-010-0595-x
DO - 10.1007/s00249-010-0595-x
M3 - Article
VL - 39
SP - 1407
EP - 1419
JO - European Biophysics Journal
JF - European Biophysics Journal
SN - 0175-7571
IS - 10
ER -