>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.
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机译:扩展的聚谷氨酰胺(polyQ)的聚集似乎是各种遗传性神经退行性疾病的原因。关于polyQ结构和诱导聚集的机理还知之甚少。我们已经使用基于谷胱甘肽 S em>-转移酶融合蛋白的模型系统在蛋白质环境中表征了polyQ的溶液结构。应用了广泛的生物物理技术。第一次,核磁共振被用来直接和选择性地观察polyQ在病理范围内的构象。我们证明,在解决方案中,polyQs具有随机线圈构象。但是,在不稳定条件下,它们的聚集行为由polyQ长度决定。
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