Interplay between Chaperones and Protein Disorder Promotes the Evolution of Protein Networks
Figure 4
Weak chaperone dependence promotes NC substitutions.
A The over-expression of GroEL in the directed evolution of enzymes reported in [6] promotes NC substitutions, thus validation the definition of NC mutations and λ. B Native substrates of the E. coli chaperonin GroEL (n = 58) do not evolve at higher ω than non-substrates (n = 216). Shown is the partial regression plot of the contribution of chaperone dependence on ω, together with 5% confidence intervals. The confidence intervals reflect the limited power of predicting a continuous variable, e.g. ω, from chaperone dependence alone. The significance of chaperone dependence is assessed by non-parametric regression analyses that explicitly include expression and disorder as confounding factors. C Native substrates of the E. coli chaperonin GroEL evolve at significantly higher λ. D Human kinases that are substrates of Hsp90 do not evolve at significantly higher ω than kinases that are not Hsp90 substrates when expression levels as confounding factor are included in the analysis. E Both strongly (n = 71) and weakly (n = 70) Hsp90 dependent kinases exhibit a significantly higher λ than non-substrates (n = 61). F Strong substrates of the yeast Hsp70 SSB (n = 648) evolve at lower ω, weak substrates (n = 310) at similar ω compared to non-substrates (n = 721). G Strong SSB substrates also evolve at lower λ, but weak substrates evolve at higher λ. Significance levels are indicated as n.s. (not significant), * (p<0.05), ** (p<0.01), and *** (p<0.001).