Fig. 1.

The active γ-secretase complex is composed of four subunits: presenilin (PS, yellow) with catalytic aspartyl residues (Asp), highly glycosylated nicastrin (NCT, violet), presenilin enhancer 2 (PEN-2, green), and anterior pharynx defective 1 (APH-1, red). In a mature complex, PS is autoendoproteolytically cleaved (stars) within a loop between TMD6 and TMD7. Both the catalytic aspartyl residues of PS are also localized within TMD6 and TMD7. Substrate binding site and active site are very close to each other. PEN-2 interacts with PS NTF. NCT/APH-1 subcomplex interacts with PS CTF