Site-Specific Fluorescence Polarization for Studying the Disaggregation of α-Synuclein Fibrils by Small Molecules
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- 作者：Conor M. Haney ; Christina L. Cleveland ; Rebecca F. Wissner ; Lily Owei ; Jaclyn Robustelli ; Malcolm J. Daniels ; Merve Canyurt ; Priscilla Rodriguez ; Harry Ischiropoulos ; Tobias Baumgart ; E. James Petersson
- 刊名：Biochemistry
- 出版年：2017
- 出版时间：February 7, 2017
- 年：2017
- 卷：56
- 期：5
- 页码：683-691
- 全文大小：500K
- ISSN：1520-4995
文摘
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.