Temperature profoundly affects ataxin-3 fibrillogenesis
Temperature profoundly affects ataxin-3 fibrillogenesis
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DOI：
10.1016/j.biochi.2012.01.002
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发表时间：
2012-04-01
期刊：
影响因子：
3.9
通讯作者：
Regonesi, Maria Elena
中科院分区：
文献类型：
--
作者：
Apicella, Alessandra;Natalello, Antonino;Regonesi, Maria Elena
当 Ataxin-3 (AT3) 携带的聚谷氨酰胺拉伸超出临界阈值时，会引发 3 型脊髓小脑共济失调。通过傅里叶变换红外光谱和原子力显微镜，我们之前表明，正常（AT3Q24）和扩展（AT3Q55）变体能够在37摄氏度下演变成低聚物和原纤维，而只有扩展形式产生不可逆聚集的原纤维，这些原纤维也与侧链谷氨酰胺氢键网络相关[Natalello等人，2017]。 （2011）公共图书馆一号。 6：e18789]。我们在此报告，当逐渐加热至 85 摄氏度时，AT3Q24 会发生与 37 摄氏度下观察到的类似的聚集；相比之下，AT3Q55 只产生大的、无定形的聚集体。我们提出了温度影响原纤维形成结果的机制的可能解释。 (C) 2012 Elsevier Masson SAS。版权所有。
Ataxin-3 (AT3) triggers spinocerebellar ataxia type 3 when it carries a polyglutamine stretch expanded beyond a critical threshold. By Fourier transform infrared spectroscopy and atomic force microscopy we previously showed that a normal (AT3Q24) and an expanded (AT3Q55) variant were capable of evolving into oligomers and protofibrils at 37 degrees C, whereas only the expanded form generated irreversibly aggregated fibrils that also were associated with a network of side-chain glutamine hydrogen bonding [Natalello et al. (2011) PLoS One. 6:e18789]. We report here that AT3Q24, when gradually heated up to 85 degrees C, undergoes aggregation similar to that observed at 37 degrees C; in contrast, AT3Q55 only generates large, amorphous aggregates. We propose a possible interpretation of the mechanism by which temperature affects the outcome of fibrillogenesis. (C) 2012 Elsevier Masson SAS. All rights reserved.