Site-specific fluorescence polarization for studying the disaggregation of α-synuclein fibrils by small molecules
Date
2017
Authors
Haney, C. M.
Cleveland, C. L.
Wissner, R. F.
Owei, L.
Robustelli, J.
Daniels, M. J.
Canyurt, M.
Rodriguez, P.
Ischiropoulos, H.
Baumgart, T.
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Source Title
Biochemistry
Print ISSN
0006-2960
Electronic ISSN
Publisher
American Chemical Society
Volume
56
Issue
5
Pages
683 - 691
Language
English
Type
Article
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Abstract
Fibrillar 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.
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Keywords
Binding sites , Fluorescence , Polarization , Proteins , Disaggregation , Fibril formation , Fibrillar aggregates , Fluorescence polarization , Local dynamics , Site-specific , Small molecules , Structural remodeling , Molecules , Polyphenol derivative , Dodecyl sulfate sodium , Epigallocatechin gallate , Fluorescent dye , Liposome , Nordihydroguaiaretic acid , Texas red , Xanthene derivative , Conformational transition , Micelle , Molecular interaction , Priority journal , Protein binding , Analogs and derivatives , Chemistry , Ddrug effects , Human , Metabolism , Molecular library , Pharmacology , Catechin , Dopamine , Masoprocol , Phosphatidylcholines , Protein aggregates , Recombinant proteins , Sodium dodecyl sulfate , Unilamellar liposomes , Xanthenes