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. Author manuscript; available in PMC: 2012 Feb 17.
Published in final edited form as: J Alzheimers Dis. 2011;25(1):3–28. doi: 10.3233/JAD-2011-101065

Fig. 2.

Fig. 2

PS/γ-secretase complex. The four components of the functional PS/γ-secretase complex are shown. PS consists of nine transmembrane domains (marked 1–9) and exerts the catalytic activity of the complex. PS topology is somewhat controversial. Here it is presented according to Kornilova et al. [241]. During maturation of the γ-secretase complex, PS undergoes endoproteolysis yielding the N-terminal (NTF) and the C-terminal fragment (CTF). The active aspartate residues in transmembrane domains 6 and 7 are indicated with sparkles. Nicastrin is a type-I transmembrane glycoprotein. Aph-1 consists of seven transmembrane domains (marked 1–7), and its membrane topology is presented according to Fortna et al. [242]. Nicastrin and Aph-1 facilitate the assembly and trafficking of γ-secretase. Pen-2, which promotes PS endoproteolysis, is a hairpin-structured protein with two transmembrane domains. According to Crystal et al. [243], both its N- and C-termini are on the luminal side of the membrane.