*2.2. EC Pairs Have More Atomic Contacts between Them than Other Pairs*

Interchain residue–residue atomic contacts have been obtained from the Protein Contacts Atlas (PCA) [51] portal for the 34 X-Ray structures. Among EC-containing complexes, 2A7U is an NMR structure so it was not included in the following residue-contact analysis. From the contact lists between the IDP chain and the relevant partner chains, the numbers of atomic contacts between each contacting residue pair have been obtained, the residue pairs have been grouped as ECs, EC residue/no-EC residue pairs and no-EC residue/no-EC residue pairs, and the numbers of atomic contacts for these three groups have been compared. Although only 7 of the 20 visible ECs of X-ray structures had atomic contacts in PCA, with a median of 5, ECs had significantly more contacts between them than contacting residue pairs in the other two groups (Figure 2A). A likely reason behind EC/no-EC pairs having significantly less contacts than no-EC/no-EC pairs is that in the EC/no-EC dataset the contacting residues of EC residues were skimmed. Their respective EC pairs were not taken into account in this dataset; still, they had less space to make contacts with other, no-EC residues. We also wanted to see how many contacts EC residues have, regardless of their partner residue. To this end, we added up the total number of atomic contacts (with all contacting partner residues) for all residues in the contact lists for the IDPs and partners separately. These values were then compared between EC and non-EC residues. We did not find significant differences neither for IDPs nor for their partners (Supplementary Figure S1). Thus, we can claim that although the individual residues of IDP-partner ECs do not have more atomic contacts than other residues, ECs taken as pairs do have more atomic contacts with each other than other residue pairs.
