Haney Conor M, Cleveland Christina L, Wissner Rebecca F, Owei Lily, Robustelli Jaclyn, Daniels Malcolm J, Canyurt Merve, Rodriguez Priscilla, Ischiropoulos Harry, Baumgart Tobias, Petersson E James
Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
Pharmacology Graduate Group, University of Pennsylvania , 3400 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, United States.
Biochemistry. 2017 Feb 7;56(5):683-691. doi: 10.1021/acs.biochem.6b01060. Epub 2016 Nov 11.
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.
蛋白质α-突触核蛋白（αS）的纤维状聚集体是帕金森病的标志性特征之一。在此，我们表明，测量αS上多个位点标记物的荧光偏振（FP），能够监测该蛋白质与胶束或囊泡结合后以及原纤维形成过程中局部动力学的变化。最为重要的是，这些位点特异性FP测量为小分子对αS原纤维的结构重塑提供了深入了解，并且有潜力用于中等通量筛选，以鉴定可用于治疗帕金森病的小分子。
