Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/99756
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dc.contributor.authorPolling, S.en
dc.contributor.authorOrmsby, A.en
dc.contributor.authorWood, R.en
dc.contributor.authorLee, K.en
dc.contributor.authorShoubridge, C.en
dc.contributor.authorHughes, J.en
dc.contributor.authorThomas, P.en
dc.contributor.authorGriffin, M.en
dc.contributor.authorHill, A.en
dc.contributor.authorBowden, Q.en
dc.contributor.authorBöcking, T.en
dc.contributor.authorHatters, D.en
dc.date.issued2015en
dc.identifier.citationNature Structural and Molecular Biology, 2015; 22(12):1008-1015en
dc.identifier.issn1545-9993en
dc.identifier.issn1545-9985en
dc.identifier.urihttp://hdl.handle.net/2440/99756-
dc.descriptionPublished online 16 November 2015en
dc.description.abstractPolyglutamine (polyGln) expansions in nine human proteins result in neurological diseases and induce the proteins' tendency to form β-rich amyloid fibrils and intracellular deposits. Less well known are at least nine other human diseases caused by polyalanine (polyAla)-expansion mutations in different proteins. The mechanisms of how polyAla aggregates under physiological conditions remain unclear and controversial. We show here that aggregation of polyAla is mechanistically dissimilar to that of polyGln and hence does not exhibit amyloid kinetics. PolyAla assembled spontaneously into α-helical clusters with diverse oligomeric states. Such clustering was pervasive in cells irrespective of visible aggregate formation, and it disrupted the normal physiological oligomeric state of two human proteins natively containing polyAla: ARX and SOX3. This self-assembly pattern indicates that polyAla expansions chronically disrupt protein behavior by imposing a deranged oligomeric status.en
dc.description.statementofresponsibilitySaskia Polling, Angelique R Ormsby, Rebecca J Wood, Kristie Lee, Cheryl Shoubridge, James N Hughes, Paul Q Thomas, Michael D W Griffin, Andrew F Hill, Quill Bowden, Till Böcking and Danny M Hattersen
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rights© 2015 Nature America, Inc. All rights reserved.en
dc.subjectAmyloiden
dc.titlePolyalanine expansions drive a shift into α-helical clusters without amyloid-fibril formationen
dc.title.alternativePolyalanine expansions drive a shift into alpha-helical clusters without amyloid-fibril formationen
dc.typeJournal articleen
dc.identifier.rmid0030040739en
dc.identifier.doi10.1038/nsmb.3127en
dc.relation.granthttp://purl.org/au-research/grants/arc/DP120102763en
dc.relation.granthttp://purl.org/au-research/grants/arc/FT120100039en
dc.relation.granthttp://purl.org/au-research/grants/arc/FT100100411en
dc.relation.granthttp://purl.org/au-research/grants/arc/FT100100560en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1049458en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/628946en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/465401en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1049459en
dc.identifier.pubid220349-
pubs.library.collectionPaediatrics publicationsen
pubs.library.teamDS03en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidShoubridge, C. [0000-0002-0157-3084]en
Appears in Collections:Paediatrics publications

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