Guanidine hydrochloride denaturation of dopamine-induced α-synuclein oligomers: a small-angle x-ray scattering study

Simple item page
dc.contributor.authorPham, CLLen_AU
dc.contributor.authorKirby, Nen_AU
dc.contributor.authorWood, Ken_AU
dc.contributor.authorRyan, Ten_AU
dc.contributor.authorRoberts, Ben_AU
dc.contributor.authorSokolova, AVen_AU
dc.contributor.authorBarnham, KJen_AU
dc.contributor.authorMasters, CLen_AU
dc.contributor.authorKnott, RBen_AU
dc.contributor.authorCappai, Ren_AU
dc.contributor.authorCurtain, CCen_AU
dc.contributor.authorRekas, Aen_AU
dc.date.accessioned2016-10-18T00:51:54Zen_AU
dc.date.available2016-10-18T00:51:54Zen_AU
dc.date.issued2013-06-4en_AU
dc.date.statistics2016-10-18en_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.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.identifier.govdoc7341en_AU
dc.identifier.issn1097-0134en_AU
dc.identifier.issue1en_AU
dc.identifier.journaltitleProteins: Structure, Function, and Bioinformaticsen_AU
dc.identifier.pagination10-21en_AU
dc.identifier.urihttp://dx.doi.org/10.1002/prot.24332en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/7779en_AU
dc.identifier.volume82en_AU
dc.language.isoenen_AU
dc.publisherWiley Online Libraryen_AU
dc.subjectX-ray diffractionen_AU
dc.subjectMelaninen_AU
dc.subjectHydrochloric aciden_AU
dc.subjectPathologyen_AU
dc.subjectCovalenceen_AU
dc.subjectToxinsen_AU
dc.subjectDopamineen_AU
dc.titleGuanidine hydrochloride denaturation of dopamine-induced α-synuclein oligomers: a small-angle x-ray scattering studyen_AU
dc.typeJournal Articleen_AU
Files
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Journal Articles