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It has recently been suggested that the concentrations of proteins in the cell are tuned towards their critical values, and that the alteration of this balance often results in misfolding diseases. This concept is intriguing because
the in vivo concentrations of proteins are closely regulated by complex cellular processes, while their critical concentrations are primarily determined by the chemical characters of their amino acid sequences. We discuss how the presence of a link between the upper levels of in vivo concentrations and critical concentrations offers an opportunity to make quantitative predictions in cell biology based on the chemical properties
of proteins.
By investigating the relationship between mRNA expression levels and protein solubility in the cell we formulate the CamEL method which enables the prediction of the maximal levels of mRNA expression in E. coli with an accuracy of 83%, and of the solubility of recombinant human proteins expressed in E. coli with an accuracy of 86%. We also report a series of relationships between GroEL/ES and DnaK/J requirements, protein abundance, aggregation propensities and mRNA expression levels. By exploiting these relationships, we can predict predict the propensity of proteins for GroEL/ES chaperonin requirements with high accuracy. |
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