Abstract
The ultimate overexpression of a protein could cause growth defects, which are known as the protein burden. However, the expression limit at which the protein-burden effect is triggered is still unclear. To estimate this limit, we systematically measured the overexpression limits of glycolytic proteins in Saccharomyces cerevisiae. The limits of some glycolytic proteins were up to 15% of the total cellular protein. These limits were independent of the proteins' catalytic activities, a finding that was supported by an in silico analysis. Some proteins had low expression limits that were explained by their localization and metabolic perturbations. The codon usage should be highly optimized to trigger the protein-burden effect, even under strong transcriptional induction. The S-S-bond-connected aggregation mediated by the cysteine residues of a protein might affect its expression limit. Theoretically, only non-harmful proteins could be expressed up to the protein-burden limit. Therefore, we established a framework to distinguish proteins that are harmful and non-harmful upon overexpression.
Highlights
Protein overexpression is sometimes harmful to cellular growth (Makanae et al, 2013; Sopko et al, 2006), and a few mechanisms that could result in overexpression-triggered growth defects have been proposed (Moriya, 2015)
We measured the expression limits of most of the 29 target proteins in low-copy conditions because the expression levels produced under these conditions were already sufficient to cause growth defects
Only non-harmful proteins can be overexpressed up to the ultimate level, or the protein-burden limit, because the expression limit of harmful proteins should be restricted by their harmful effects
Summary
Protein overexpression is sometimes harmful to cellular growth (Makanae et al, 2013; Sopko et al, 2006), and a few mechanisms that could result in overexpression-triggered growth defects have been proposed (Moriya, 2015). The ultimate overexpression of a protein could be harmful for cellular growth, because it monopolizes and depletes limited resources that are involved in protein production, such as ribosomes and aminoacyl-tRNAs (Gong et al, 2006; Shachrai et al, 2010; Vind et al, 1993). This phenomenon is known as the protein burden/cost effect (Kafri et al, 2016; Snoep et al, 1995). Proteins that have no harmful effects on cellular functions can be overexpressed up to a level that causes protein-
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