*2.3. ECs Are Significantly Closer to Each Other than Randomly Paired IDP–Partner Interface Residues*

We were also interested in the distance distribution of ECs. For the pairs with PCA atomic contacts, we took the shortest atomic contact as residue–residue distance, while for the rest of the visible ECs (including the ones in the NMR structure 2A7U) we calculated the minimal residue–residue distances using PyMOL (Supplementary Table S3). We compared the distance distribution so obtained to an equivalent reference distance distribution of randomly selected and subsequently paired IDP and partner residues picked from the same interfaces and found that ECs are highly significantly closer in space than the randomly paired interchain interface residue pairs (Figure 2B). The sampling of randomly paired interface residues was carried out 100 times and their distances were consistently significantly larger than those of ECs (*p* < 0.01). The descriptive distribution features (minimum, 1st quantile, mean, median, 3rd quantile, maximum) of the 100 samples have shown an average standard deviation of 2.31 which we interpret as low variation among the random samples. 18/22 visible ECs were closer than 8 Å, two were between 8 and 10 Å far, and only two had >10 Å distances (Figure 2C). The latter two were assigned as outliers by R, they probably represent mistakenly identified pairs (or have larger distances due to other reasons [52]) and thus have been handled as outliers and excluded from distance comparisons (Figure 2B). One of the outliers is the 183Q-226W IDP-partner EC pair in the RseA/RseB (PDB: 3M4W) complex as indicated in Figure 1. The other outlier is the sole EC pair (74D-133Y) identified in the CP12/Glyceraldehyde-3-phosphate dehydrogenase (PDB: 3B1K) complex. Therefore, the latter complex is left without any reliable ECs, and thus it is not shown in Figure 1.

**Figure 2.** Atomic contacts and distances of ECs. (**A**) The numbers of atomic contacts connecting EC pairs according to PCA compared to those of other contacting residue pairs. Pairwise comparisons were done with Mann–Whitney U test with the corresponding p-values indicated; (**B**) the minimum distances between visible EC pairs are compared to those of randomly selected and paired IDP–partner interface residues; (**C**) histogram showing the distribution of minimum distances between visible ECs; (**D**) the proportions of main secondary structure element types (H—helix, S—strand, L—loop) are compared between EC and no-EC residues for IDPs and partners separately. In the boxplots stars (\*) indicate the average values of the datasets.
