Effect of EGCG on Fe(III)-induced conformational transition of silkfibroin, a model of protein related to neurodegenerative diseases
Effect of EGCG on Fe(III)-induced conformational transition of silkfibroin, a model of protein related to neurodegenerative diseases
复制标题
EGCG 对 Fe(III) 诱导的丝素蛋白构象转变的影响，丝素蛋白是一种与神经退行性疾病相关的蛋白质模型
DOI：
10.1002/bip.22752
复制
发表时间：
2016
期刊：
影响因子：
2.9
通讯作者：
Ping Zhou
中科院分区：
文献类型：
--
作者：
Lihui Xu;Sidong Tu;Congheng Chen;Juan Zhao;Yuan Zhang;Ping Zhou
据报道，淀粉样蛋白的异常聚集在神经退行性疾病的病因学中起关键作用。研究表明，过量的三价铁离子与淀粉样蛋白的错误折叠有关，并且（-）-表没食子儿茶素没食子酸酯（EGCG）是一种良好的金属离子螯合剂，对淀粉样蛋白的聚集具有抑制作用。因此，EGCG被认为是治疗神经退行性疾病的潜在候选药物。然而，EGCG抑制淀粉样蛋白聚集的作用机制仍不清楚。丝素蛋白（SF）与淀粉样蛋白在某些氨基酸序列和原纤化动力学方面具有相似性。因此，在这项工作中，我们使用SF作为蛋白质的模型，通过浊度测定，硫磺素T（ThT）荧光光谱，拉曼光谱，原子力显微镜（AFM）研究Fe（III）和EGCG对构象转变的影响。我们证明，低浓度的Fe（III）离子促进β-折叠构象的形成，而高浓度的Fe（III）离子抑制SF的进一步聚集。表没食子儿茶素没食子酸酯可以显着抑制Fe（III）诱导的SF的构象转变，并呈剂量依赖性地减少β折叠构象的数量。这些发现提供了关于EGCG作为预防和治疗神经退行性疾病的潜在药物的重要信息。Fe（III）能促进丝原纤维（SF）从无规卷曲向β-折叠的构象转变，而表没食子儿茶素没食子酸酯（EGCG）则抑制Fe（III）诱导的SF β-折叠聚集。2016.© 2015 Wiley Periodicals，Inc.生物聚合物105：100-107，2016
The abnormal aggregation of amyloid proteins is reported to play a critical role in the etiology of neurodegenerative disorders. Studies have shown that excessive ferric irons are associated with the misfolding of amyloid proteins, and that (‐)‐epigallocatechin gallate (EGCG) is a good metallic ion chelator with inhibitory effect on the aggregation of amyloid proteins. EGCG has been thus considered as a potential drug candidate for the treatment of neurodegenerative diseases. However, the mechanism of action for EGCG in inhibition of aggregation of amyloid proteins is still remaining unclear. Silk fibroin (SF) shares similarities with amyloid proteins in some amino acid sequences and fibrillation kinetics. In this work, therefore, we used SF as a model of protein to investigate the effects of Fe(III) and EGCG on conformational transition by using turbidity assay, thioflavin T (ThT) fluorescence spectroscopy, Raman spectroscopy, and atomic force microscope (AFM). We demonstrated that low concentration of Fe(III) ions promoted the formation of β‐sheet conformers, while high concentration of Fe(III) ions inhibited further aggregation of SF. EGCG could significantly inhibit the conformational transition of SF when induced by Fe(III), and decrease the amount of β‐sheet conformers dose‐dependently. The findings provide important information regarding to EGCG as a potential agent for the prevention and treatment of neurodegenerative diseases. Fe(III) can accelerate the conformation transition of silk fibrion (SF) from random coil into β‐sheet, while (‐)‐epigallocatechin gallate (EGCG) inhibits Fe(III)‐induced β‐sheet aggregation of SF., 2016. © 2015 Wiley Periodicals, Inc. Biopolymers 105: 100–107, 2016