Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom.
Cold Spring Harb Perspect Biol. 2019 Dec 2;11(12):a033845. doi: 10.1101/cshperspect.a033845.
One of the major functions of the protein homeostasis system is to maintain proteins in their soluble states, and indeed several human disorders are associated with the aberrant aggregation of proteins. An active involvement of the protein homeostasis system is necessary to avoid aggregation because proteins are expressed at levels close to their solubility limits, hence being poorly soluble. The mechanisms by which the protein homeostasis system acts to control protein aggregation are, however, still not known in much detail. To facilitate systematic investigations of these mechanisms, we describe here the CamSol method of predicting protein solubility, and illustrate its initial applications. We anticipate that with the advent of powerful proteomics and transcriptomic methods, in combination with the use of the CamSol method and related approaches to predict the solubility and other biophysical properties of proteins, it will become possible to increase our understanding of the principles of protein homeostasis related to the maintenance of the proteome in its soluble form.
蛋白质动态平衡系统的主要功能之一是维持蛋白质处于可溶状态,事实上,几种人类疾病都与蛋白质的异常聚集有关。为了避免聚集,蛋白质动态平衡系统必须发挥积极作用,因为蛋白质的表达水平接近其溶解度极限,因此溶解度较差。然而,蛋白质动态平衡系统控制蛋白质聚集的机制仍不太清楚。为了促进对这些机制的系统研究,我们在这里描述了预测蛋白质溶解度的 CamSol 方法,并说明了其初步应用。我们预计,随着强大的蛋白质组学和转录组学方法的出现,结合使用 CamSol 方法和相关方法来预测蛋白质的溶解度和其他生物物理特性,将有可能增加我们对与维持蛋白质组以可溶性形式存在相关的蛋白质动态平衡原则的理解。