Elucidation of molecular mechanism of polyglutamine protein induced dysfunction of mitochondrial membrane and dynamics

聚谷氨酰胺病是一种由蛋白质错误折叠和聚集引起的神经退行性疾病。在本研究中，我们分析了模型聚谷氨酰胺蛋白的构象变化对其酶功能的影响以及与模型脂膜的相互作用。我们发现聚谷氨酰胺蛋白的酶活性受到可溶性淀粉样蛋白构象的抑制。这一发现表明，多聚谷氨酰胺蛋白的构象转变抑制了生理功能，并导致细胞功能障碍。

Polyglutamine disease is neurodegenerative disorder caused by protein misfolding and aggregation. In this study, we analyzed the effect of conformational change of model polyglutamine protein to its enzymatic function and interaction with model lipid membrane. We show the enzymatic activity of polyglutamine protein is suppressed by soluble amyloidogenic conformer. This finding indicates that conformational transitions of polyglutamine protein inhibit physiological function and induce cellular dysfunction.