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Assembly and activation of the γ-secretase complex. Nicastrin and Aph-1 form a stable subcomplex (step 1), followed by addition of presenilin (step 2). Interaction of Pen-2 with TMD4 of presenilin (step 3) triggers autoproteolysis of presenilin into NTF and CTF subunits (step 4) to form γ-secretase capable of cleaving substrates.
