脱化加速了粉样蛋白的形成,并改变了氨酸纤维结构
Emily B Dunkelberger1, Lauren E Buchanan, Peter Marek
1Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706-1396, United States.
Journal of the American Chemical Society
|June 28, 2012
概括
脱化加速了氨酸粉样蛋白的形成,并改变了纤维结构,形成了进一步聚合的种子. 这种修饰会影响蛋白质的稳定性,并且可以通过同位素标记的红外光谱检测.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 生物物理学的生物物理.
背景情况:
- 阿斯巴拉金和谷氨胺的脱化是一种常见的翻译后修饰,影响蛋白质结构和聚合.
- 粉样蛋白形成,涉及到2型糖尿病,涉及蛋白质,如氨酸.
- 由于方法上的挑战,对脱化对粉样纤维的影响的结构研究是有限的.
研究的目的:
- 调查除化对氨酸粉样蛋白形成的动力学和结构的影响.
- 了解脱化如何影响氨酸粉样纤维的结构完整性.
主要方法:
- 检查了除化对氨酸粉样蛋白形成动力学的影响.
- 利用特定地点的同位素标记和二维红外 (2D IR) 光谱.
- 分析了氨酸纤维的结构模型,并与除化部位结合使用.
主要成果:
- 脱化加速了氨酸粉样蛋白的形成,并产生能够诱导未经修改的氨酸聚合的种子.
- 含有脱胺胺氨基素的纤维具有降低的β-片含量,在N-和C-终端区域都有破坏.
- 在N端β薄膜区域的除氧化似乎导致了广泛的结构破坏.
结论:
- 脱化是一种翻译后的修改,它改变了氨酸纤维结构,同时保持了播种能力.
- 以同位素标记的红外光谱学提供了一种方法来监测脱化诱导的样本降解和粉样纤维的结构变化.
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