波谱学杂志2016，Vol.33Issue(2)：179-187,9.DOI:10.11938/cjmr20160201
乙酰化修饰抑制-synuclein的纤维化聚集
Lysine Acetylation Inhibits-Synuclein Fibrillation
摘要
Abstract
Fibrils of intrinsically disordered proteina-synuclein (a-syn) are hallmarks of Parkinson’s disease. Electrostatic interactions are known to contribute significantly ona-syn aggregation. Here we studied howa-syn conformation and fibrillation were affected by changing the net charge of the protein via acetylation of lysine side chains. NMR spectroscopy results showed that lysine-acetylateda-syn remained disordered, and showed a more extended conformation, relative to wild-type protein. Acetylation inhibiteda-syn fibrillation, revealed by thioflavin (ThT) fluorescence assay. The N- and C-terminals of the acetylated protein were highly negative charged, causing increased exposure of the non-amyloid-b component (NAC) region. It is proposed that, with the charge distribution in the acetylated protein, electrostatic repulsion, instead of hydrophobic effect, may contribute predominately to the aggregation. This charge-effect mechanism may constitute a new strategy to inhibita-syn fibrillation.关键词
液体核磁共振(liquid-state NMR)/乙酰化修饰/纤维化聚集/-synucleinKey words
liquid-state NMR/acetylation/fibrillation/α-synuclein分类
数理科学引用本文复制引用
翟紫凝,吴琼,李从刚..乙酰化修饰抑制-synuclein的纤维化聚集[J].波谱学杂志,2016,33(2):179-187,9.基金项目
Ministry of Science and Technology of China (2013CB910200) （2013CB910200）
National Natural Science Foundation of China (21173258,21120102038 and 21221064) （21173258,21120102038 and 21221064）
