血清粉样蛋白A截断和它们的上层结构性之间的关系
Noa Rubin1, Emanuel Perugia, Sharon G Wolf
1Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel 76100.
Journal of the American Chemical Society
|March 12, 2010
概括
从血清粉样蛋白A (SAA) 形成的粉样蛋白纤维可以表现出明显的左手或右手超结构性. 这种由序列影响的开关改变了分子结构和FTIR光谱,影响了粉样蛋白的形成.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 粉样蛋白是与20多种疾病相关的蛋白质聚合物.
- 粉样纤维具有交叉β动图,β链垂直于纤维轴.
- 现有的模型描述了特定的粉样蛋白结构,但缺乏全面了解性作用.
研究的目的:
- 为了研究粉样蛋白中超结构性性,分子结构和分子性之间的相关性.
- 探索与相同核心序列的截断血清粉样蛋白A (SAA) 如何形成不同的粉样蛋白结构.
- 为了确定特定的氨基酸突变对粉样纤维性的影响.
主要方法:
- 截断的血清粉样蛋白A (SAA) 的合成和表征.
- 使用像X射线衍射 (隐含) 这样的技术分析超结构性性.
- 里埃变换红外光谱 (FTIR) 用于分析分子结构和键.
主要成果:
- 截断的SAA酸SAA2-6),SAA1-11和大多数SAA2-9) 形成左侧的粉样纤维,与β-sheet原纤维模型一致.
- 具有C末端突变的SAA{1-12},SAA{2-12}和SAA{1-12}变体形成了右侧螺旋性粉样纤维.
- 与左侧纤维相比,右侧纤维在FTIR光谱中显示出红移的胺I峰值,表明结构差异.
结论:
- 短的amyloidogenic片段可以折叠成不同的amyloid结构,具有不同的超结构性.
- C终端区域和特定突变显著影响SAA粉样纤维的螺旋手性.
- 氨基原核序列在孤立时,与它们在全长蛋白中的作用相比,可能采用不同的结构.
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