Figure 1.

(A) Schematic representation of the holoprotein of human APP₆₉₅ including the relative position of the α-, β- and γ-secretase cleavage sites. (B) Domain organization of APP: the E1 region consists of the N-terminal growth factor-like domain (GFLD) and the following copper-binding domain (CuBD). The E1 region is linked via the acidic region to the carbohydrate domain, which contains the two N-glycosylation sites of the ectodomain (red spheres). The carbohydrate domain can be subdivided into the E2 domain, also called central APP domain (CAPPD), and a linker or juxtamembrane domain. The carbohydrate domain is followed by the transmembrane and the APP intracellular domain (AICD). Aβ indicates the amyloid β-peptide sequence. The Kunitz-type protease inhibitor domain (KPI), which is present in APP₇₅₁ and APP₇₇₀, and the Ox2 sequence, which is present in APP₇₇₀, are shown above their insertion site. (C) Known stable structures of APP.