通过结构同类物来导航下坡蛋白质折叠模式
Athi N Naganathan1, Peng Li, Raúl Perez-Jimenez
1Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Ramiro de Maeztu 9, Madrid 28040, Spain.
Journal of the American Chemical Society
|August 12, 2010
概括
蛋白质下坡折叠,以低的自由能量障碍为特征,显示平衡特征与折叠率成比例. 对BBL和PDD等同类蛋白质的比较分析证实了这种关系,有助于研究折叠屏障.
科学领域:
- 生物物理学的生物物理.
- 蛋白质动力学 蛋白质动力学
- 结构生物学是结构生物学.
背景情况:
- 折叠在低自由能障碍 (<或=3RT) 上的蛋白质被归类为下坡折叠.
- 下坡折叠的特点是广泛的平衡展开,随着折叠障碍的减少,复杂性增加.
- 预计超快速折叠 (微秒),但速率-平衡关系受到蛋白质大小和拓学的影响.
研究的目的:
- 直接比较两个结构同类物,BBL和PDD的动力学和平衡展开.
- 为了研究下坡折叠蛋白质中速率和平衡特征之间的关系,考虑结构和尺寸效应.
- 为了验证超快速折叠蛋白质的平衡分析提供了关于自由能量障碍的直接信息.
主要方法:
- 对BBL和PDD的动力学和平衡展开的比较分析.
- 折叠/展开速度和平衡展开特征的直接比较.
- 对利率与平衡关系的结构和规模效应的分析.
主要成果:
- 在335K时,BBL在1微秒内折叠/展开,表现出强烈的下坡折叠平衡特征.
- 类似尺寸的结构同类PDD,折叠/展开速度约为8倍,并显示减弱的下坡平衡特征.
- 下坡折叠的平衡特征与结构和尺寸因素正常化时的折叠率变化成正比.
结论:
- 下坡折叠的平衡标志与折叠速度有量性的联系,即使对于超快的工艺.
- 这一发现挑战了对蛋白质折叠的传统观点,认为它仅仅是一个高度激活的过程.
- 对同源蛋白质的平衡动力学研究对于理解折叠障碍及其序列,功能和进化决定因素是有价值的.
相关概念视频
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