ANSTO Publications Online >
Journal Publications >
Journal Articles >
Please use this identifier to cite or link to this item:
|Title: ||Guanidine hydrochloride denaturation of dopamine-induced α-synuclein oligomers: A small-angle X-ray scattering study|
|Authors: ||Pham, CLL|
|Keywords: ||X-RAY DIFFRACTION|
|Issue Date: ||31-Aug-2013|
|Publisher: ||Wiley Online Library|
|Citation: ||Pham, C. L. L., Kirby, N., Wood, K., Ryan, T., Roberts, B., Sokolova, A., . . . Rekas, A. (2014). Guanidine hydrochloride denaturation of dopamine-induced alpha-synuclein oligomers: A small-angle X-ray scattering study. Proteins-Structure Function and Bioinformatics, 82(1), 10-21. doi: http://dx.doi.org/10.1002/prot.24332|
|Abstract: ||Alpha-synuclein (α-syn) forms the amyloid-containing Lewy bodies found in the brain in Parkinson's disease. The neurotransmitter dopamine (DA) reacts with α-syn to form SDS-resistant soluble, non-amyloid, and melanin-containing oligomers. Their toxicity is debated, as is the nature of their structure and their relation to amyloid-forming conformers of α-syn. The small-angle X-ray scattering technique in combination with modeling by the ensemble optimization method showed that the un-reacted native protein populated three broad classes of conformer, while reaction with DA gave a restricted ensemble range suggesting that the rigid melanin molecule played an important part in their structure. We found that 6 M guanidine hydrochloride did not dissociate α-syn DA-reacted dimers and trimers, suggesting covalent linkages. The pathological significance of covalent association is that if they are non-toxic, the oligomers would act as a sink for toxic excess DA and α-syn; if toxic, their stability could enhance their toxicity. We argue it is essential, therefore, to resolve the question of whether they are toxic or not. © 2013,Wiley Periodicals, Inc.|
|Appears in Collections:||Journal Articles|
Files in This Item:
There are no files associated with this item.
Items in APO are protected by copyright, with all rights reserved, unless otherwise indicated.