Figure 3. Quantitative scanning of C99‐Bpa substrate interaction sites with γ‐secretase.

Quantitative crosslinking analysis revealed V44, L49, M51, and L52 as major interactions sites of C99 with γ‐secretase with high crosslinking efficiencies ranging from ~2 to 8% of input. While the PS1 NTF was bound by C99 over nearly the whole range of residues, only very few residues bound to PS1 CTF. Several residues in the substrate N‐terminal extracellular domain bound to NCT. PEN‐2‐binding residues clustered in the membrane‐flanking extracellular and intracellular domains of C99.

Bars denote the mean ± SE (n = 3).