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Figure 4


Fig. 4. Temporal sequence of interactions leading to {gamma}-secretase complex formation. The earliest step in complex assembly is probably the association of NCT (green) with APH1 (blue) in the ER. From then on two `pathways' are proposed, depending on the experimental approaches used. (A) Full-length PS1 (yellow) might bind to NCT-APH1, this is followed by recruitment of PEN2 (red), which promotes endoproteolysis and stabilisation of the full complex. (B) Alternatively, full-length PS1 might first bind to PEN2, leading to endoproteolysis and binding to the pre-existing NCT-APH1 subcomplex.





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