Fig. 4: 3D presentation of selected positions.

a Glu404 (yellow) stabilizes the E-D-loop by hydrogen bonds to Tyr390 (pink). The substitution Glu404Lys destabilizes the loop. b Illustration of the highly conserved Val673 (raspberry) backbone hydrogen bonds to Phe655 (pink). The substitution Val673Ala destabilizes the E-D-loop and thereby the cadherin domain. c Electrostatic interactions between Leu979 (aquamarine; red arrow) and Asp972 and interactions with the Ca²⁺-ions are illustrated. Substituting Leu979 with phenylalanine will cause steric interference with Asp972 and Asn886. d The amino acid Asp1201 (yellow stick) interacts via backbone hydrogen bonds with Leu1203, Thr1204, and Asn1205 (pink) stabilizing the Ca²⁺-binding domain. The Asp1201Asn substitution causes steric interference with Asn1205, destabilizing the Ca²⁺ binding domain. Conserved Amino acids are indicated in yellow. e Thr1472 (yellow) form backbone hydrogen bonds to Gly1525 and hydroxyl bond to Glu1474 and Arg1838 (all in pink). The Thr1472Ser substitution will abolish the hydroxyl bond and destabilize the structure. f Leu1479 (yellow) forms hydrogen bonds to Leu1494 and Gly1268 (both pink). The substitution Leu1479His will result in steric interference with Thr1472 and Gly1477, destabilizing the highly conserved laminin-neurexin globular cysteine disulfide bridge between Cys1840 and Cys1870 (not highlighted). g The Val2338 (red) and its polar bonds to Phe2253 (light blue) are illustrated. Red arrows depict the autoproteolytic site between β-sheet 19 and the highly conserved β-sheet 20 (orange). Polar bonds stabilizing the GPS domain is illustrated by blue dots. The substitution Val2338Ile is predicted to hamper autoproteolysis. The two pairs of conserved disulfide bonds are illustrated by yellow sticks. h The Ala2486Pro substitution will cause a kink and is incompatible with alpha helical structure. Crystal structure PDB numbers and the associated protein domains of the individual figures are described in the Results section. Hydrogen and polar bonds are illustrated by dashed yellow lines.