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dc.contributor.authorLowe, R
dc.contributor.authorPountney, DL
dc.contributor.authorJensen, PH
dc.contributor.authorGai, WP
dc.contributor.authorVoelcker, NH
dc.date.accessioned2017-05-03T15:03:35Z
dc.date.available2017-05-03T15:03:35Z
dc.date.issued2004
dc.date.modified2009-01-13T07:11:05Z
dc.identifier.issn0961-8368
dc.identifier.urihttp://hdl.handle.net/10072/16541
dc.description.abstracta-Synuclein filaments are the major component of intracytoplasmic inclusion bodies characteristic of Parkinson's disease and related disorders. The process of a-synuclein filament formation proceeds via intermediate or protofibrillar species, each of which may be cytotoxic. Because high levels of calcium(II) and other metal ions may play a role in disease pathogenesis, we investigated the influence of calcium and other metals on a-synuclein speciation. Here we report that calcium(II) and cobalt(II) selectively induce the rapid formation of discrete annular a-synuclein oligomeric species. We used atomic force microscopy to monitor the aggregation state of a-synuclein after 1 d at 4àin the presence of a range of metal ions compared with the filament formation pathway in the absence of metal ions. Three classes of effect were observed with different groups of metal ions: (1) Copper(II), iron(III), and nickel(II) yielded 0.8-4 nm spherical particles, similar to a-synuclein incubated without metal ions; (2) magnesium(II), cadmium(II), and zinc(II) gave larger, 5-8 nm spherical oligomers; and, (3) cobalt(II) and calcium(II) gave frequent annular oligomers, 70-90 nm in diameter with calcium(II) and 22-30 nm in diameter with cobalt(II). In the absence of metal ions, annular oligomers ranging 45-90 nm in diameter were observed after 10 d incubation, short branched structures appeared after a further 3 wk and extended filaments after 2-3 mo. Previous studies have shown that a-synuclein calcium binding is mediated by the acidic C terminus. We found that truncated a-synuclein (1-125), lacking the C-terminal 15 amino acids, did not form annular oligomers upon calcium addition, indicating the involvement of the calcium-binding domain.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent183381 bytes
dc.format.extent45087 bytes
dc.format.extent45087 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.format.mimetypetext/plain
dc.languageEnglish
dc.language.isoeng
dc.publisherCold Spring Harbor Press
dc.publisher.placeUSA
dc.publisher.urihttp://www.proteinscience.org/
dc.relation.ispartofpagefrom3245
dc.relation.ispartofpageto3252
dc.relation.ispartofissue12
dc.relation.ispartofjournalProtein Science
dc.relation.ispartofvolume13
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchTheory of computation
dc.subject.fieldofresearchOther information and computing sciences
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode4613
dc.subject.fieldofresearchcode4699
dc.titleCalcium(II) selectively induces α-synuclein annular oligomers via interaction with the C-terminal domain
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyright© 2004 Protein Society. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.date.issued2004
gro.hasfulltextFull Text
gro.griffith.authorPountney, Dean L.


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