Fig. 1

Amyloid precursor protein. A The extracellular (e.c.) part of APP consists of the E1 domain [containing the N-terminal growth factor-like domain (GFLD) and the copper-binding domain (CuBD)], the acidic region, and the E2 domain. The juxtamembrane (j.m.) region connects the e.c. portion to the transmembrane (TM) segment. The C-terminus is cytosolically aligned at the end of the cytosolic APP intracellular domain (AICD). In the TM domain, glycines G633-634 form a kink that is locally destabilizes the secondary structure. The red lines show the angles characteristic of the orientation of APP in the membrane (see text). B Amino acid sequence of the TM segment and AICD of APP. Cleavage sites for α-, β-, and γ- secretase (including the ε-site) are indicated. Light orange—amino acids buried in the hydrophobic zone of the bilayer, dark orange and red—glycines forming glycine zippers (dimerization motifs). Glycines 37/38 of C99 (after β-cleavage) correspond to G633/634 of APP (A). Adjusted according to [193, 195, 201, 203, 256, 338]