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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Catechin / analogs & derivatives*
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Catechin / chemistry
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Catechin / pharmacology
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Dopamine / chemistry*
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Dopamine / pharmacology
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Fluorescence Polarization
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Fluorescent Dyes / chemistry
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Humans
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Masoprocol / chemistry*
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Masoprocol / metabolism
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Phosphatidylcholines / chemistry
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Protein Aggregates / drug effects*
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Recombinant Proteins / chemistry
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Small Molecule Libraries / chemistry*
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Small Molecule Libraries / pharmacology
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Sodium Dodecyl Sulfate / chemistry
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Unilamellar Liposomes / chemistry
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Xanthenes / chemistry
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alpha-Synuclein / chemistry*
Substances
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Fluorescent Dyes
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Phosphatidylcholines
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Protein Aggregates
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Recombinant Proteins
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Small Molecule Libraries
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Unilamellar Liposomes
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Xanthenes
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alpha-Synuclein
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Sodium Dodecyl Sulfate
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Masoprocol
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Texas red
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Catechin
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epigallocatechin gallate
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1,2-oleoylphosphatidylcholine
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Dopamine