在α-β平行蛋白折叠过程中,外路物种的大量形成是由于 (非) 原生结构元素在未折叠的分子中对接
Sanne M Nabuurs1, Adrie H Westphal, Carlo P M van Mierlo
1Laboratory of Biochemistry, Wageningen University, Dreijenlaan 3, 6703 HA Wageningen, The Netherlands.
Journal of the American Chemical Society
|December 5, 2008
概括
蛋白质的展开揭示了apoflavodoxin中短暂的螺旋结构. 在未折叠状态下,这些非原生相互作用意外地促进了离路径折叠,阻碍了高效的蛋白质折叠.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 蛋白质折叠的动力学
背景情况:
- 了解蛋白质折叠需要详细了解未折叠状态和折叠中间体.
- 病态蛋白质聚合与特定折叠中间体的形成有关.
研究的目的:
- 在残留水平上研究瓜尼丁化解折的阿波弗拉夫多克辛的结构特征.
- 为了阐明在apoflavodoxin折叠过程中形成脱离路径的螺旋式折叠中间体的原因.
主要方法:
- 异质核核核磁共振光谱学被用来描述未折叠的阿波弗拉夫毒素.
- 远紫外线循环二极化 (CD) 光谱法用于确认二次结构群体.
主要成果:
- 在3.4M的化剂下,未折叠的阿波弗拉夫多克辛表现出四个暂时有序的区域,灵活性受限.
- 其中三个地区形成阿尔法螺旋环 (人口约10%),其中一个地区采用非本土结构.
- 这些有序段之间的疏水性相互作用导致非本地对接,促进出路物种的形成.
结论:
- 在α-β平行蛋白的未折叠状态下,形状预组织可以促进脱离路径的物种形成.
- 在未折叠的状态下,非本地相互作用与生产性的路径折叠相竞争.
- 这项研究提供了对未折叠状态在蛋白质折叠和聚合中的作用的见解.
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