Fig. 4: Features of proteins with short total half-lives.

A Scatter plot of protein total half-lives for C-lim, P-lim, and N-lim conditions. The total half-lives of rapidly degrading proteins are typically similar under different nutrient limitations. Three proteins with the shortest average total half-lives are marked. Short-lived proteins are enriched for transcriptional regulators (BH p-value = 4E–4). B The 24 proteins with the shortest mean total half-lives. For eight of these proteins (in blue), we could not find any prior literature evidence for degradation, and six (marked with *) contain Fe–S clusters (BH p-value = 0.048). (C, E, F) For all the boxplots, the box extends from the first quartile to the third quartile of the data, with a line at the median. The whiskers extend from the box to the farthest data point lying within 1.5× the interquartile range from the box. C Smaller proteins have shorter total half-lives. Left: Box plot of total half-lives averaged over all the nutrient limitations for low and high molecular weight (MW) proteins (n = 2864 total proteins, p-value = 1E–11, Mann–Whitney U, one-sided). Right: Fold enrichment of low versus high MW proteins as a function of total half-life. D Comparison of the proteome-wide N-terminus amino acid residues obtained from this study and prior literature. The size of the marker indicates the number of proteins with a particular residue. E No correlation between the N-terminal protein residue and protein total half-lives (N-end rule). Left: Distribution of the N-terminus residues for actively degrading and stable proteins. Right: Box plots of total half-lives for the destabilizing and stabilizing residues on their N-terminus (p-value: 0.99, Mann–Whitney U, one-sided, n = 373 total proteins). F Disordered proteins tend to have shorter total half-life⁹⁹. Left: The Espritz algorithm classified proteins as ordered or disordered. Right: Box plot of total half-lives for disordered and ordered proteins (n = 2865 total protein, p-value = E–18, Mann–Whitney U, one-sided). G Fold enrichment of disordered versus ordered proteins as a function of total half-life for the WT (olive) and triple protease KO (brown) cells. Rapidly turning over proteins are enriched for the disordered category. This enrichment becomes more pronounced when three proteases are knocked out.