Vilar Marçal, Wang Lei, Riek Roland
Neurodegeneration Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
Methods Mol Biol. 2012;849:185-98. doi: 10.1007/978-1-61779-551-0_13.
The elucidation of the structure of amyloid fibrils and related aggregates is an important step towards understanding the pathogenesis of diseases such as Alzheimer's and Parkinson's, which feature protein misfolding and/or aggregation. However, the large size and poor solubility of amyloid-like fibrils make them resistant to high-resolution structure determination. Here, we describe the use of hydrogen-deuterium exchange coupled with NMR as an indirect strategy to determine the folding regions of amyloid-forming proteins at residue level resolution.
阐明淀粉样纤维及相关聚集体的结构是理解诸如阿尔茨海默病和帕金森病等以蛋白质错误折叠和/或聚集为特征的疾病发病机制的重要一步。然而，淀粉样样纤维的大尺寸和低溶解性使其难以进行高分辨率的结构测定。在此，我们描述了使用氢-氘交换结合核磁共振作为一种间接策略，以残基水平分辨率确定淀粉样形成蛋白的折叠区域。
