Haney, C. M.Cleveland, C. L.Wissner, R. F.Owei, L.Robustelli, J.Daniels, M. J.Canyurt, M.Rodriguez, P.Ischiropoulos, H.Baumgart, T.Petersson, E. J.2018-04-122018-04-1220170006-2960http://hdl.handle.net/11693/37311Fibrillar aggregates of the protein α-synuclein (αS) are one of the hallmarks of Parkinson’s disease. Here, we show that measuring the fluorescence polarization (FP) of labels at several sites on αS allows one to monitor changes in the local dynamics of the protein after binding to micelles or vesicles, and during fibril formation. Most significantly, these site-specific FP measurements provide insight into structural remodeling of αS fibrils by small molecules and have the potential for use in moderate-throughput screens to identify small molecules that could be used to treat Parkinson’s disease. © 2016 American Chemical Society.EnglishBinding sitesFluorescencePolarizationProteinsDisaggregationFibril formationFibrillar aggregatesFluorescence polarizationLocal dynamicsSite-specificSmall moleculesStructural remodelingMoleculesPolyphenol derivativeDodecyl sulfate sodiumEpigallocatechin gallateFluorescent dyeLiposomeNordihydroguaiaretic acidTexas redXanthene derivativeConformational transitionMicelleMolecular interactionPriority journalProtein bindingAnalogs and derivativesChemistryDdrug effectsHumanMetabolismMolecular libraryPharmacologyCatechinDopamineMasoprocolPhosphatidylcholinesProtein aggregatesRecombinant proteinsSodium dodecyl sulfateUnilamellar liposomesXanthenesArticle10.1021/acs.biochem.6b01060