Figure 1. Cleavage of C99‐Bpa constructs by γ‐secretase.

1. Schematic representation of the genetic approach to site specifically incorporate the photoactivatable amino acid derivative Bpa into C99.
2. C99‐Bpa constructs remain essentially cleavage competent. Numbers denote the relative γ‐secretase cleavage efficiencies of C99‐Bpa substrates as calculated from the AICD/C99‐Bpa ratios relative to that of WT C99, which was set to 1. Inefficiently cleaved substrates (cleavage efficiency below 20%) were mostly found for Bpa substitutions in extramembranous domains. Specificity of substrate cleavage was confirmed by the inhibition of AICD formation in the presence of L‐685,458. Residues of the TMD are highlighted in orange here and elsewhere where appropriate.
3. Values obtained in (B) were additionally plotted. Yellow line indicates the cleavage efficiency of WT C99, which was set to 1. ECD, extracellular domain; ICD, intracellular domain.