Kinjo Akira R, Takada Shoji
PRESTO, Japan Science and Technology Corporation, Kobe University, Kobe 675-8501, Japan.
Phys Rev E Stat Nonlin Soft Matter Phys. 2002 Sep;66(3 Pt 1):031911. doi: 10.1103/PhysRevE.66.031911. Epub 2002 Sep 24.
Proteins are neither purified nor diluted inside the living cell. Thus it is indispensable to take into account various interactions between the protein of interest and other macromolecules for understanding the properties of proteins in physiological conditions. Here we focus on excluded volume interactions which are omnipresent in dense or crowded solutions of proteins and macromolecules or "crowding agents." A protein solution with macromolecular crowding agents is modeled by means of a density functional theory. Effects of macromolecular crowding on protein aggregation and stability are investigated in particular. Phase diagrams are obtained in various parameter spaces by solving the equation of state. Two generic features are found: the addition of the crowding agent (1) enhances the aggregation of the denatured proteins, and (2) stabilizes the native protein unless the aggregation occurs. The present theory is qualitatively in good agreement with experimental observations and unifies previous theories regarding the crowding effects on protein stability and aggregation.
在活细胞内，蛋白质既不会被纯化也不会被稀释。因此，为了理解蛋白质在生理条件下的特性，考虑目标蛋白质与其他大分子之间的各种相互作用是必不可少的。在这里，我们关注的是在蛋白质、大分子或“拥挤剂”的密集或拥挤溶液中普遍存在的排除体积相互作用。具有大分子拥挤剂的蛋白质溶液通过密度泛函理论进行建模。特别研究了大分子拥挤对蛋白质聚集和稳定性的影响。通过求解状态方程在各种参数空间中获得相图。发现了两个一般特征：添加拥挤剂（1）增强了变性蛋白质的聚集，（2）稳定了天然蛋白质，除非发生聚集。本理论在定性上与实验观察结果高度一致，并统一了先前关于拥挤对蛋白质稳定性和聚集影响的理论。
