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dc.contributor.authorPham, CLL-
dc.contributor.authorKirby, N-
dc.contributor.authorWood, K-
dc.contributor.authorRyan, T-
dc.contributor.authorRoberts, B-
dc.contributor.authorSokolova, AV-
dc.contributor.authorBarnham, KJ-
dc.contributor.authorMasters, CL-
dc.contributor.authorKnott, RB-
dc.contributor.authorCappai, R-
dc.contributor.authorCurtain, CC-
dc.contributor.authorRekas, A-
dc.identifier.citationPham, C. L. L., Kirby, N., Wood, K., Ryan, T., Roberts, B., Sokolova, A., Barnham, K. J., Masters, C. L., Knott, R. B., Cappai, R., Curtain, C. C., & 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:10.1002/prot.24332en_AU
dc.description.abstractAlpha-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.en_AU
dc.publisherWiley Online Libraryen_AU
dc.subjectX-ray diffractionen_AU
dc.subjectHydrochloric aciden_AU
dc.titleGuanidine hydrochloride denaturation of dopamine-induced α-synuclein oligomers: A small-angle X-ray scattering studyen_AU
dc.typeJournal Articleen_AU
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