Figure 4

LNS domains as a versatile toolbox for protein-protein interactions. The diagram shows a ribbon structure of αLNS6 (PDB ID: 2R1D) representing the lowest common denominator of the six neurexin LNS folds; it is used here to highlight specific features among the individual domains. The fold is formed by 14 β-strands (β1 to 14), which are generally tightly connected. In αLNS6/βLNS, β10 (blue) can be displaced by an alternatively spliced insert at SS#4 (red). The synopsis also shows that positions of splice sites SS#2 (green) from αLNS2, SS#3 (orange) from αLNS4, and SS#4 from αLNS6 are all in vicinity of the corresponding Ca²⁺-binding site. The splice insert in SS#4 participates in Ca²⁺ coordination, while an insert in the SS#3 domain might prevent Ca²⁺ association in adjacent αLNS3. In the αLNS3 domain, the β4/β5 loop (magenta) is prolonged and can be interpreted as a permanent splice insert that interacts with the insert in SS#3. These β-loop variations individually shape each LNS domain around the Ca²⁺-binding site suitable to mediate specific LNS-protein or LNS-glycan interactions. LNS, laminin-neurexin-sex hormone binding globulin.