Fig. 6: Proteins with long NFDs are associated with co-translational misfolding and aggregation. | Nature Communications

Fig. 6: Proteins with long NFDs are associated with co-translational misfolding and aggregation.

From: Native Fold Delay and its implications for co-translational chaperone binding and protein aggregation

Fig. 6

A Total NFD of actively translated proteins in S. cerevisiae grouped based on their co-translational interaction with Ssb (bound: n = 1913; not bound: n = 910)30. Ssb-bound proteins are further stratified as soluble (n = 1495) or aggregated (n = 418) in SSBΔ cells. B NFD across nascent chains aligned to the start of Ssb binding footprints with peak widths between 5–11 aas, in proteins that aggregate or remain soluble in SSBΔ cells. The dataset includes 1917 Ssb binding sites in aggregating proteins and 5415 in soluble proteins. Lines represent the median NFD value at each position, while shaded regions indicate the 95% bootstrapped confidence intervals. C Number of APRs per 100aa in soluble (n = 1495) and aggregated (n = 418) Ssb-bound proteins in SSBΔ cells. D, E Proportion of APR starting sites across codon bins relative to the start of Ssb binding footprints with peak widths between 5-11 aa in proteins that aggregate (D) or remain soluble (E) in SSBΔ cells. A two-sided Fisher’s exact test with FDR correction was used to compare the proportion of APR starting sites in the Ssb binding region against the other regions. Asterisks indicate statistical significance (defined below). F Total NFD of yeast proteins under physiological conditions (n = 107) or upon exposure to arsenite stress (n = 140) compared to background (MS proteome; n = 1179)48. G Total NFD of proteins co-translationally ubiquitinated under physiological conditions (n = 600)51. As background we use the translatome (n = 1790) reported by Willmund et al.30. In box plots (A, C, F, and G), the box shows interquartile range, the line indicates the median and whiskers span 1.5 times the interquartile range. Notches around the median indicate an approximate 95% confidence interval. Statistical significance was determined using a two-sided unpaired Wilcoxon test with Bonferroni correction for multiple comparisons. Statistical significance: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns = not significant.

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