Zheng Jie, Ma Buyong, Nussinov Ruth
Basic Research Program, SAIC-Frederick, Inc., Center for Cancer Research Nanobiology Program, NCI-Frederick, Frederick, MD 21702, USA.
Phys Biol. 2006 Oct 3;3(3):P1-4. doi: 10.1088/1478-3975/3/3/P01.
Amyloid fibrils characterized as highly intractable thread-like species are associated with many neurodegenerative diseases. Although neither the mechanism of amyloid formation nor the origin of amyloid toxicity is currently completely understood, the detailed three-dimensional atomic structures of the yeast protein Sup35 and Abeta amyloid protein determined by recent experiments provide the first and important step towards the comprehension of the pathogenesis and aggregation mechanisms of amyloid diseases. By analyzing these two amyloid peptides which have available crystal structures and other amyloid sequences with proposed structures using computational simulations, we delineate three common features in amyloid organizations and amyloid structures. These could contribute to an improved understanding of the molecular mechanism of amyloid formation, the nature of the aggregation driving forces that stabilize these structures and the development of potential therapeutic agents against amyloid diseases.
淀粉样纤维被认为是高度难以处理的丝状物质，与许多神经退行性疾病有关。尽管目前尚未完全了解淀粉样蛋白形成的机制和淀粉样蛋白毒性的起源，但最近实验确定的酵母蛋白Sup35和β淀粉样蛋白的详细三维原子结构为理解淀粉样疾病的发病机制和聚集机制迈出了重要的第一步。通过使用计算模拟分析这两种具有可用晶体结构的淀粉样肽以及其他具有推测结构的淀粉样序列，我们描绘了淀粉样蛋白组织和淀粉样结构中的三个共同特征。这些特征有助于更好地理解淀粉样蛋白形成的分子机制、稳定这些结构的聚集驱动力的性质以及针对淀粉样疾病的潜在治疗药物的开发。
