芳香侧链在整体膜蛋白的折叠和热力学稳定性中的作用
Heedeok Hong1, Sangho Park, Ricardo H Flores Jiménez
1Department of Molecular Physiology and Biological Physics, University of Virginia Health System, Charlottesville, VA 22908-0736, USA.
Journal of the American Chemical Society
|June 15, 2007
概括
芳香残留物显著稳定了像OmpA.这样的膜蛋白. 它们在膜接口上的聚类为蛋白质折叠和稳定提供了关键的驱动力,其中托,氨酸和氨酸的具体贡献.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 膜生物物理学 膜生物物理学
背景情况:
- 芳香残留物在膜蛋白中常见,在膜-水界面.
- 之前的研究使用模型来了解它们在蛋白质折叠中的作用.
- 这些残留物对实际膜蛋白稳定性的直接贡献仍未得到量化.
研究的目的:
- 为了研究接口芳香残留物对外膜蛋白OmpA的热力学稳定性的贡献.
- 量化OmpA.A.中各个芳香残留物 (托,氨酸,氨酸) 的稳定性贡献.
- 分析芳香-芳香侧链相互作用对蛋白质稳定性的影响.
主要方法:
- OmpA蛋白的广泛的位点定向突变发生.
- 在脂质双层中进行平衡折叠实验.
- 双重突变周期分析以评估侧链相互作用.
主要成果:
- 隔离的界面型酸盐为OmpA稳定性贡献了 -2.0 kcal/mol,铁酸盐 -2.6 kcal/mol,氨酸 -1.0 kcal/mol.
- 这些贡献与Wimley-White尺度一致,氨酸的贡献高于预测.
- 芳香-芳香侧链相互作用 (-1.0至-1.4 kcal/mol) 在<6 Å的分离时变得显著.
结论:
- 接口芳香残留物对于β-桶膜蛋白的热力学稳定性至关重要.
- 芳香-芳香相互作用在残留物非常接近时,对稳定性有显著的贡献.
- 膜接口上的芳香残留物的聚类代表了不可分割的膜蛋白折叠和稳定性的未被认可的驱动力.
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