Masino Laura, Kelly Geoff, Leonard Kevin, Trottier Yvon, Pastore Annalisa
National Institute for Medical Research, The Ridgeway, NW7 1AA, London, UK.
FEBS Lett. 2002 Feb 27;513(2-3):267-72. doi: 10.1016/s0014-5793(02)02335-9.
Aggregation of expanded polyglutamine (polyQ) seems to be the cause of various genetic neurodegenerative diseases. Relatively little is known as yet about the polyQ structure and the mechanism that induces aggregation. We have characterised the solution structure of polyQ in a proteic context using a model system based on glutathione S-transferase fusion proteins. A wide range of biophysical techniques was applied. For the first time, nuclear magnetic resonance was used to observe directly and selectively the conformation of polyQ in the pathological range. We demonstrate that, in solution, polyQs are in a random coil conformation. However, under destabilising conditions, their aggregation behaviour is determined by the polyQ length.
扩展型聚谷氨酰胺（polyQ）的聚集似乎是各种遗传性神经退行性疾病的病因。目前对于polyQ的结构以及诱导聚集的机制了解相对较少。我们使用基于谷胱甘肽S-转移酶融合蛋白的模型系统，在蛋白质环境中对polyQ的溶液结构进行了表征。应用了多种生物物理技术。首次使用核磁共振直接且选择性地观察病理范围内polyQ的构象。我们证明，在溶液中，polyQ呈无规卷曲构象。然而，在不稳定条件下，它们的聚集行为由polyQ长度决定。
