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dc.contributor.authorLemkau, LRen_US
dc.contributor.authorComellas, Gen_US
dc.contributor.authorLee, SWen_US
dc.contributor.authorRikardsen, LKen_US
dc.contributor.authorWoods, WSen_US
dc.contributor.authorGeorge, JMen_US
dc.contributor.authorRienstra, CMen_US
dc.date.accessioned2013-12-18T09:24:21Z
dc.date.available2012-10-17en_US
dc.date.issued2013en_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/4901
dc.descriptionPMCID: PMC3591419
dc.descriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.description.abstractParkinson's disease (PD) is pathologically characterized by the presence of Lewy bodies (LBs) in dopaminergic neurons of the substantia nigra. These intracellular inclusions are largely composed of misfolded α-synuclein (AS), a neuronal protein that is abundant in the vertebrate brain. Point mutations in AS are associated with rare, early-onset forms of PD, although aggregation of the wild-type (WT) protein is observed in the more common sporadic forms of the disease. Here, we employed multidimensional solid-state NMR experiments to assess A53T and E46K mutant fibrils, in comparison to our recent description of WT AS fibrils. We made de novo chemical shift assignments for the mutants, and used these chemical shifts to empirically determine secondary structures. We observe significant perturbations in secondary structure throughout the fibril core for the E46K fibril, while the A53T fibril exhibits more localized perturbations near the mutation site. Overall, these results demonstrate that the secondary structure of A53T has some small differences from the WT and the secondary structure of E46K has significant differences, which may alter the overall structural arrangement of the fibrils.en_US
dc.format.extente49750 - ?en_US
dc.languageengen_US
dc.relation.ispartofPLoS Oneen_US
dc.subjectAmino Acid Sequenceen_US
dc.subjectHumansen_US
dc.subjectLewy Bodiesen_US
dc.subjectMolecular Sequence Dataen_US
dc.subjectMutant Proteinsen_US
dc.subjectMutationen_US
dc.subjectNuclear Magnetic Resonance, Biomolecularen_US
dc.subjectParkinson Diseaseen_US
dc.subjectProtein Structure, Secondaryen_US
dc.subjectalpha-Synucleinen_US
dc.titleSite-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.en_US
dc.typeArticle
dc.identifier.doi10.1371/journal.pone.0049750en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/23505409en_US
pubs.issue3en_US
pubs.notesNot knownen_US
pubs.publication-statusPublisheden_US
pubs.volume8en_US
dcterms.dateAccepted2012-10-17en_US


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