School of Applied and Engineering Physics, Cornell University, Ithaca, NY, USA.
Phys Biol. 2012 Oct;9(5):056005. doi: 10.1088/1478-3975/9/5/056005. Epub 2012 Aug 29.
Both increased temperature and moderate concentrations of fluorinated alcohols enhance aggregation of the Parkinson's disease-associated protein α-synuclein (αS). Here, we investigate the secondary structural rearrangements induced by heating and trifluoroethanol [TFE]. At low TFE concentrations, CD spectra feature a negative peak characteristic of disordered polypeptides near 200 nm and a slight shoulder around 220 nm suggesting some polyproline-II content. Upon heating, these peaks weaken, while a weak negative signal develops at 222 nm. At high TFE concentrations, the spectra show distinct minima at 208 and 222 nm, indicative of considerable α-helical structure, which diminish upon heating. We observe a crossover between the low-TFE and high-TFE behavior near 15% TFE, where we previously showed that a partially helical intermediate is populated. We postulate that the protein is well solvated by water at low TFE concentrations and by TFE at high TFE concentrations, but may become desolvated at the crossover point. We discuss the potential roles and interplay of desolvation and helical secondary structure in driving αS aggregation.
温度升高和中等浓度的氟醇均会增强帕金森病相关蛋白α-突触核蛋白（αS）的聚集。在这里，我们研究了加热和三氟乙醇[TFE]引起的二级结构重排。在低 TFE 浓度下，CD 光谱在 200nm 附近具有特征性的无序多肽负峰，在 220nm 附近有轻微的肩峰，表明存在一些聚脯氨酸-II 含量。加热时，这些峰减弱，而在 222nm 处出现较弱的负信号。在高 TFE 浓度下，光谱在 208nm 和 222nm 处显示出明显的最小值，表明存在相当大的α-螺旋结构，这些结构在加热时减少。我们在低 TFE 和高 TFE 行为之间的 15% TFE 附近观察到交叉，我们之前曾表明在该点存在部分螺旋中间体。我们假设在低 TFE 浓度下，蛋白质被水很好地溶剂化，而在高 TFE 浓度下，蛋白质被 TFE 溶剂化，但在交叉点可能会去溶剂化。我们讨论了去溶剂化和螺旋二级结构在驱动αS 聚集中的潜在作用和相互作用。
