Driving amyloid toxicity in a yeast model by structural changes: a molecular approach
Driving amyloid toxicity in a yeast model by structural changes: a molecular approach
复制标题
DOI：
10.1096/fj.08-125724
复制
发表时间：
2009-07-01
期刊：
影响因子：
4.8
通讯作者：
Cullin, Christophe
中科院分区：
文献类型：
--
作者：
Berthelot, Karine;Immel, Francoise;Cullin, Christophe
淀粉样蛋白聚集途径是一个多步骤的过程，许多体外研究强调了特定中间体在各种淀粉样蛋白疾病的细胞毒性中的作用。在之前的研究中，我们产生了无害的模型淀粉样蛋白Het-s（218-289）的酵母毒性突变体（M8）。在本研究中，我们比较了野生型（WT）和毒性突变体在分子水平上的聚集特征。两种蛋白形成纤维淀粉样蛋白聚集体，但具有不同的染料结合特性和x射线衍射模式。有毒淀粉样蛋白形成非常不寻常的短（80纳米）无分枝纤维，在透射电子显微镜下可见。傅里叶变换红外光谱表明，M8 β -片基本上呈平行和反平行混合结构，而WT蛋白则以平行结构为主。因此，细胞毒性可能与有毒淀粉样蛋白在新的聚集途径中的组装有关。-Berthelot， K., Immel， F., Gean， J., Lecomte， S., Oda， R., Kauffmann， B., Cullin， C.通过结构变化驱动酵母模型中的淀粉样蛋白毒性：一种分子方法。财经杂志23,2254-2263 （2009）
The amyloid aggregation pathway is a multistep process, and many in vitro studies have highlighted the role of particular intermediates in the cellular toxicity of various amyloid diseases. In a previous study, we generated a yeast toxic mutant (M8) of the harmless model amyloid protein Het-s(218-289). In this study, we compared the aggregation characteristics of the wild-type (WT) and the toxic mutant at the molecular level. Both proteins formed fibrillar amyloid aggregates but with different dye-binding properties and X-ray diffraction patterns. The toxic amyloid formed very unusual short (80 nm) unbranched fibers visible on transmission electron microscopy. Fourier transform infrared spectroscopy demonstrated that M8 beta-sheets were essentially organized into a mixed parallel and antiparallel structure, whereas the WT protein displayed a predominantly parallel organization. Cellular toxicity may therefore be related to assembly of the toxic amyloid in a new aggregation pathway.-Berthelot, K., Immel, F., Gean, J., Lecomte, S., Oda, R., Kauffmann, B., Cullin, C. Driving amyloid toxicity in a yeast model by structural changes: a molecular approach. FASEB J. 23, 2254-2263 (2009)