Figure 7

Distinct contacts at CNTN–amyloid interfaces.A, sequence alignment of APP/APPb, APLP1, and APLP2. In the limited segments shown here, the sequences of human, mouse, chicken APP, and zebrafish APPb are identical. Similarly, the sequences of human, mouse, and zebrafish APLP1 are identical, and the sequences of human, mouse, chicken, and zebrafish APLP2 are identical. Strictly conserved residues are shown in black. The magenta dot indicates the position of A126, which is conserved in APP and APLP1, but replaced by a valine in APLP2. The numbering above the sequences corresponds to amino acid positions in chicken APP, which is identical in mouse and human APP. A more extensive alignment is shown in Fig. S2. B, detailed view of the chicken CNTN4–APP interface with translucent surfaces highlighting APP residue A126 nestled against M749, Y761, and Y763 in CNTN4. Dashed lines indicate hydrogen bonds between T751, Y761, and S124. C, detailed view of the zebrafish CNTN4–APPb interface highlighting interactions between APPb residue A128 and CNTN4 residues M752, Y764, and F766. Note that compared with the chicken sequence, the sequence of chicken CNTN4 is offset by three amino acids. D, detailed view of the chicken CNTN3–APP interface. Here, A126 contacts I649, Y661, and F663. Dashed lines indicate hydrogen bonds between T651, Y661, and APP residue S124. E, detailed view of the mouse CNTN5–APP interface. Here, APP residue A126 contacts the aliphatic portion of K821 and Y835 but not F833. Dashed lines indicate hydrogen bonds between K821 and Y835 in CNTN5 and between K823 in CNTN5 and S124 in APP. F, detailed view of the zebrafish CNTN4–APLP2 interface. The alanine residue found in APP is replaced by a valine in APLP2 (V133), which contacts M752, Y764, and F766. The side chain of M752 has swung away from the position it occupies in the chicken CNTN4–APP and zebrafish CNTN4–APPb complexes. APLP2, amyloid beta precursor like protein 2; APP, amyloid precursor protein; CNTN, contactin.