蛋白质折叠驱动二硫化物形成
Pallav Kosuri1, Jorge Alegre-Cebollada2, Jason Feng2
1Graduate Program in Biochemistry & Molecular Biophysics, Columbia University, New York, NY 10027, USA; Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Cell
|November 13, 2012
概括
蛋白质二硫化异构酶 (PDI) 有助于蛋白质折叠. 新的方法揭示了PDI有利于在折叠晚期的本地二硫化物键,防止错误折叠,并使共翻译氧化折叠成为可能.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 蛋白质折叠 蛋白质的折叠
背景情况:
- 蛋白二硫化异构酶 (PDI) 对于含有二硫化键的蛋白质的氧化折叠至关重要.
- 通过PDI实现原生蛋白质氧化的精确反应序列仍然不完全理解.
研究的目的:
- 开发一种用于同时测量二硫化物键形成和蛋白质折叠的新技术.
- 阐明PDI在氧化折叠途径中的作用,并确定防止错误折叠的机制.
主要方法:
- 开发一种允许独立量化二硫化物形成和蛋白质折叠动态的技术.
- 对氧化折叠途径早期和晚期阶段的分析.
主要成果:
- 非原生二硫化物键在折叠过程的早期形成,并可能导致蛋白质错误折叠.
- 特定的PDI域在折叠的后期阶段促进本地二硫化物键的形成.
- 提出了一种对转换性氧化折叠的模型,其中PDI作为基板折叠时释放的短暂因素.
结论:
- PDI的功能是特定阶段的,有利于在折叠晚期的本地二硫化物键,以确保正确的蛋白质结构.
- 拟议的共翻译氧化折叠机制为PDI在各种蛋白质基质上的活性提供了一般的解释.
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