Tartaglia Gian Gaetano, Pechmann Sebastian, Dobson Christopher M, Vendruscolo Michele
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
J Mol Biol. 2009 May 1;388(2):381-9. doi: 10.1016/j.jmb.2009.03.002. Epub 2009 Mar 10.
Each step in the process of gene expression, from the transcription of DNA into mRNA to the folding and posttranslational modification of proteins, is regulated by complex cellular mechanisms. At the same time, stringent conditions on the physicochemical properties of proteins, and hence on the nature of their amino acids, are imposed by the need to avoid aggregation at the concentrations required for optimal cellular function. A relationship is therefore expected to exist between mRNA expression levels and protein solubility in the cell. By investigating such a relationship, we formulate a method that enables the prediction of the maximal levels of mRNA expression in Escherichia coli with an accuracy of 83% and of the solubility of recombinant human proteins expressed in E. coli with an accuracy of 86%.
基因表达过程中的每一步,从DNA转录为mRNA到蛋白质的折叠和翻译后修饰,都受到复杂的细胞机制调控。与此同时,为了避免在细胞最佳功能所需浓度下发生聚集,对蛋白质的物理化学性质(进而对其氨基酸性质)施加了严格条件。因此,预计mRNA表达水平与细胞中蛋白质溶解度之间存在某种关系。通过研究这种关系,我们制定了一种方法,该方法能够以83%的准确率预测大肠杆菌中mRNA的最大表达水平,并以86%的准确率预测在大肠杆菌中表达的重组人蛋白质的溶解度。