Figure 1.
Constructing a proteomic growth model.
(A) The average % growth rate difference relative to the ‘wt’ strain in each pair (figure produced using previously published data) [4]. Error bars show +/- one standard deviation. (B) Log relative protein abundance measurements vs. growth rate for 3 example proteins. ‘NDE1’ is repressed in strains with decreased growth rate. ‘RPP2A’ is unresponsive to changing relative growth rates. ‘HSP82’ is induced in strains with decreased growth rate. Colors correspond to strain pairs in (A). Error bars show +/- one standard deviation. (C) Slopes for three example proteins from (B) multiplied by a conversion factor (see Methods S1) to allow direct comparison between our slopes (across relative % growth differences; grey) and slopes found previously (across absolute growth differences; black) [6]. We use unconverted slopes to predict growth differences. Error bars display +/- standard error on the slope.
Figure 2.
A proteomic growth model predicts small growth defects induced by protein misfolding.
(A) To select the set of proteins that best correlate with growth, we chose an R2 cutoff of 0.367, or 0.371 for a set that excludes UPR-cyto proteins (inset). (B) The predicted growth differences between paired strains, when each pair is held out from the dataset used to calibrate the proteomic growth model, fall within one standard deviation of each experimental measurement [4]. The UPR-cyto excluding model generates similar predictions (inset). Both models’ predictions have smaller standard deviations (vertical error) than growth measurements (horizontal error).
Figure 3.
Most classes of proteins do not respond to small growth perturbations induced by protein misfolding.
Expected differences in protein abundance levels are inferred from transcript data [7] (A & B) or from our proteomic data when each strain pair is held out (C), while assuming a linear response to growth. Only proteins for which we expect a significant response are plotted (i.e., proteins for which the expected fold change +/- observed error does not include 1.0 with p < 0.05). Fold changes in abundance are shown for the misfolded protein-expressing (growth-perturbed) member of each strain pair relative to the wt-expressing strain, colors represent positive (green) or negative (red) correlations with faster growth, and horizontal lines represent median values. (A) Most GRR proteins do not show the expected response to our growth perturbation. (B) Ribosomal proteins do not significantly or consistently differ in abundance between paired strains, even when the relative growth difference between strains exceeds 3% (YFPm4). (C) UPR-cyto protein abundance levels match expectations. Note that YFPm4 generates a smaller expected median UPR-cyto response despite inducing a larger growth defect because it contains data from only 2 replicate experiments and the most responsive proteins were not sampled.