Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA.
FEBS J. 2011 Oct;278(20):3868-83. doi: 10.1111/j.1742-4658.2011.08186.x. Epub 2011 Jun 13.
Several protein misfolding diseases are associated with the conversion of native proteins into ordered protein aggregates known as amyloid. Studies of amyloid assemblies have indicated that non-native proteins are responsible for initiating aggregation in vitro and in vivo. Despite the importance of these species for understanding amyloid disease, the structural and dynamic features of amyloidogenic intermediates and the molecular details of how they aggregate remain elusive. This review focuses on recent advances in developing a molecular description of the folding and aggregation mechanisms of the human amyloidogenic protein β(2)-microglobulin under physiologically relevant conditions. In particular, the structural and dynamic properties of the non-native folding intermediate I(T) and its role in the initiation of fibrillation and the development of dialysis-related amyloidosis are discussed.
几种蛋白质错误折叠疾病与天然蛋白质转化为有序蛋白质聚集体（称为淀粉样蛋白）有关。淀粉样蛋白组装体的研究表明，非天然蛋白质负责在体外和体内引发聚集。尽管这些物质对于理解淀粉样蛋白疾病很重要，但淀粉样蛋白中间产物的结构和动态特征以及它们聚集的分子细节仍然难以捉摸。这篇综述重点介绍了在生理相关条件下，对人类淀粉样蛋白β(2)-微球蛋白折叠和聚集机制进行分子描述方面的最新进展。特别是，讨论了非天然折叠中间体 I(T)的结构和动态特性及其在纤维形成起始和透析相关淀粉样变性发展中的作用。
