Extended Data Fig. 4: Aggregate size distribution shifts in response to experimental perturbation. | Nature Structural & Molecular Biology

Extended Data Fig. 4: Aggregate size distribution shifts in response to experimental perturbation.

From: Nucleation seed size determines amyloid clearance and establishes a barrier to prion appearance in yeast

Extended Data Fig. 4

The aggregate size distributions revealed by our deterministic model (shaded) shift in response to inhibition of Sup35 synthesis (a, b) or Hsp104-mediated fragmentation (c, d) after 90 min (solid, unshaded),180 min (dashed, unshaded), 270 min (dotted, unshaded) or at its steady-state (gray, unshaded) for strains propagating [PSI+]Strong with a seed size of 5 (a, c) or [PSI+]Weak with a seed size of fifteen (b, d). e, The distribution of aggregate sizes before (Xi, solid black) and after (Ci(t), dashed black) t minutes of inhibition of Sup35 synthesis is shown. The shift in the size distribution, S(t), is quantified as the area between the curves when Ci(t) > Xi (shaded area). f, The size distribution of Sup35 aggregates from a strain propagating [PSI+]Weak with a seed size of five (shaded) shifts upon inhibition of Sup35 synthesis for 90 min (solid, unshaded), 180 min (dashed, unshaded), 270 min (dotted, unshaded) or at its steady-state (gray, unshaded). g, and h, The shifts in aggregate size distribution over a range of fragmentation and conversion rates that match the steady-state soluble level of Sup35 were monitored at 90 min (solid), 180 min (dashed), 270 min (dotted) and steady-state (gray) for a strain propagating [PSI+]Weak with a seed size of five (g) or fifteen (h). The x-axis shows the fragmentation rate scaled to the strain-specific value in Supplementary Table 2 (vertical black line). While [PSI+]Weak with a seed size of five (g) shifts slowly to its steady-state distribution, [PSI+]Weak with a seed size of fifteen (h) rapidly reaches is steady-state distribution, matching our empirical observations (Fig. 4a).

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