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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
在细胞染色体c中His26的质子化触发了微秒的β-片形成和血暴露:对亡的含义
Gurusamy Balakrishnan1, Ying Hu, Thomas G Spiro
1Department of Chemistry, Princeton University, Princeton, New Jersey 08544, USA.
Journal of the American Chemical Society
|October 26, 2012
概括
细胞染色体c可逆地展开成β片结构,破坏其血红蛋白键并获得过氧化酶活性. 这一过程涉及特定的质子化事件,可能与亡相关的心脂蛋白过氧化有关.
科学领域:
- 生物化学 生物化学
- 蛋白质动力学 蛋白质动力学
- 频谱学是一种光谱学方法.
背景情况:
- 细胞染色体c (cyt c) 是细胞亡中的一个关键蛋白质.
- 它的过氧化酶活性与心脂蛋白过氧化有关.
- 了解细胞的展开对于其生物学作用至关重要.
研究的目的:
- 为了研究细胞染色体c在低pH下展开的机制.
- 描述结构变化及其与功能变化的相关性.
- 阐明特定残留物和结构元素在展开过程中的作用.
主要方法:
- 紫外共振拉曼 (UVRR) 光谱检测二次结构.
- 温度跳跃 (T跳跃) 与UVRR相结合,用于时间分辨率测量.
- 芳香残留物和血 propionate 相互作用的分析.
主要成果:
- 在pH值3的加热会诱导局部,可逆的cytoc.
- 展开将转向和螺旋转换为β片结构,而不是随机的线圈.
- Met80-heme键的破坏和芳香残留物的改变方向表明了heme的移位.
- His26的质子化破坏了它与Pro44的相互作用,启动了展开的级联.
- 确定了β片形成和Trp59重定向的时间常数 (0.2,3.9,67μs).
结论:
- 展开的机制涉及特定的质子和二次结构变化,导致血红素暴露和过氧化酶活性.
- 这种机制可能与细胞因子介导的细胞因子死亡期间的心血管胺过氧化有关.
- 通过His26-Pro44相互作用定的40s Ω循环,在细胞展开过程中起到关键的"折叠"作用.
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