Mapping the electrostatic surface of the two proteins provides evidence on the observed binding mode: a cluster of negatively charged residues formed by Asp113, Asp136, Asp137 and Asp183 in FLRT3-LRR complements the positively charged Arg273, Arg292, Arg294 and in LPHN3-OLF (Figure 5A). Moreover, several hydrogen bonds and salt bridges are observed in the main interface (Table S3, related to Figure 4) added by hydrophobic and stacking contacts involving aromatic side chains, such as Phe160 from FLRT3-LRR observed in a π-stacking with Tyr245 from LPHN3-OLF (see below). Conversely, the C-terminal region of the concave face in FLRT3-LRR and the facing area in LPHN3-OLF do not seem to be in contact, probably because they are both positively charged and likely to repel each other (Figure 5A).
