Lund P
School of Biological Sciences, University of Birmingham, Edgbaston, UK.
Bioessays. 1994 Apr;16(4):229-31. doi: 10.1002/bies.950160404.
The process of protein folding in the cell is now known to depend on the action of other proteins. These proteins include molecular chaperones, which interact non-covalently with proteins as they fold and improve the final yields of active protein in the cell. The precise mechanism by which molecular chaperones act is obscure. Experiments reported recently show that for one molecular chaperone (Cpn60, typified by the E. coli protein GroEL), the folding reaction is driven by cycles of binding and release of the co-chaperone Cpn10 (known as GroES in E. coli). These alternate with binding and release of the unfolded protein substrate. These cycles come about because of the opposite effects of Cpn10 and unfolded protein on the Cpn60 complex: the former stabilises the ADP-bound state of Cpn60, whereas the latter stimulates ADP-ATP exchange. This model proposes that the substrate protein goes through multiple cycles of binding and release, and is released into the cavity of the Cpn60 complex where it can undergo folding without interacting with other nearby folding intermediates. This is consistent with the ability of Cpn60 proteins to enhance folding by blocking pathways to aggregation.
现在已知细胞中蛋白质折叠的过程依赖于其他蛋白质的作用。这些蛋白质包括分子伴侣，它们在蛋白质折叠时与蛋白质非共价相互作用，并提高细胞中活性蛋白质的最终产量。分子伴侣发挥作用的确切机制尚不清楚。最近报道的实验表明，对于一种分子伴侣（以大肠杆菌蛋白GroEL为代表的Cpn60），折叠反应是由共伴侣Cpn10（在大肠杆菌中称为GroES）的结合和释放循环驱动的。这些循环与未折叠蛋白质底物的结合和释放交替进行。这些循环的产生是由于Cpn10和未折叠蛋白质对Cpn60复合物具有相反的作用：前者稳定Cpn60的ADP结合状态，而后者刺激ADP-ATP交换。该模型提出，底物蛋白经历多个结合和释放循环，并被释放到Cpn60复合物的腔中，在那里它可以进行折叠而不与附近的其他折叠中间体相互作用。这与Cpn60蛋白通过阻断聚集途径来增强折叠的能力是一致的。
