Province Key Laboratory of Animal Resource and Epidemic Disease Prevention, School of Life Science, Liaoning University , Shenyang 110036, China.
J Agric Food Chem. 2015 Feb 11;63(5):1347-51. doi: 10.1021/jf505277e. Epub 2015 Feb 3.
Previous studies have reported that (-)-epigallocatechin-3-gallate (EGCG), the most abundant flavonoid in green tea, can bind to unfolded native polypeptides and prevent conversion to amyloid fibrils. To elucidate whether this antifibril activity is specific to disease-related target proteins or is more generic, we investigated the ability of EGCG to inhibit amyloid fibril formation of amyloidogenic mutant chicken cystatin I66Q, a generic amyloid-forming model protein that undergoes fibril formation through a domain swapping mechanism. We demonstrated that EGCG was a potent inhibitor of amyloidogenic cystatin I66Q amyloid fibril formation in vitro. Computational analysis suggested that EGCG prevented amyloidogenic cystatin fibril formation by stabilizing the molecule in its native-like state as opposed to redirecting aggregation toward disordered and amorphous aggregates. Therefore, although EGCG appears to be a generic inhibitor of amyloid-fibril formation, the mechanism by which it achieves such inhibition may be specific to the target fibril-forming polypeptide.
先前的研究报告指出，绿茶中含量最丰富的黄酮类化合物 (-)-表没食子儿茶素-3-没食子酸酯 (EGCG) 可以与未折叠的天然多肽结合，防止其转化为淀粉样纤维。为了阐明这种抗纤维活性是否特异性针对与疾病相关的靶蛋白，或者更具普遍性，我们研究了 EGCG 抑制淀粉样蛋白形成的能力，研究对象为具有淀粉样蛋白形成能力的突变鸡半胱氨酸蛋白酶抑制剂 I66Q，这是一种通用的淀粉样蛋白形成模型蛋白，它通过结构域交换机制发生纤维形成。我们证明了 EGCG 是体外淀粉样蛋白形成的有效抑制剂。计算分析表明，EGCG 通过稳定分子处于类似天然的状态来防止淀粉样蛋白原胱抑素纤维的形成，而不是将聚集物重新引导到无定形和无定形的聚集物中。因此，尽管 EGCG 似乎是一种通用的淀粉样纤维形成抑制剂，但它实现这种抑制的机制可能是针对靶纤维形成多肽的特异性。
