Kinjo Akira R, Takada Shoji
PRESTO, Japan Science and Technology Corporation, Kobe University, Kobe, Japan.
Biophys J. 2003 Dec;85(6):3521-31. doi: 10.1016/S0006-3495(03)74772-9.
The living cell is inherently crowded with proteins and macromolecules. To avoid aggregation of denatured proteins in the living cell, molecular chaperones play important roles. Here we introduce a simple model to describe crowded protein solutions with chaperone-like species based on a dynamic density functional theory. As predicted by others, our simulations show that macromolecular crowding enhances the association of proteins and chaperones. However, when the intrinsic folding rate of the protein is slow, it is possible that crowding also enhances aggregation of proteins. The results of simulation suggest that, when the concentration of the crowding agent is as high as that in the cell, the association of the protein and unbound chaperone becomes correlated with the aggregation process, and that the protein-bound chaperones efficiently destroy the potential nuclei of aggregates and thus prevent the aggregation.
活细胞内天然地充满了蛋白质和大分子。为避免活细胞中变性蛋白质的聚集，分子伴侣发挥着重要作用。在此，我们基于动态密度泛函理论引入一个简单模型，以描述含有类伴侣物种的拥挤蛋白质溶液。正如其他人所预测的那样，我们的模拟表明大分子拥挤增强了蛋白质与伴侣的结合。然而，当蛋白质的固有折叠速率较慢时，拥挤也有可能增强蛋白质的聚集。模拟结果表明，当拥挤剂的浓度与细胞内浓度一样高时，蛋白质与未结合伴侣的结合与聚集过程相关，并且与蛋白质结合的伴侣能有效破坏潜在的聚集体核，从而防止聚集。
