Clipping APP

Several secretase enzymes break amyloid-beta precursor protein into its component parts. Beta-secretase, shown here from PDB entry 1fkn, makes the cut that releases the large portion outside the cell. It is a typical aspartyl protease, similar to the pepsin that digests proteins in your stomach. This structure has a small peptide in the active site, colored green here, and the enzyme is normally found tethered to the cell surface by a short extension, not seen in the crystal structure. Gamma-secretase, not shown, makes the cut at the bottom of the amyloid-beta peptide. It is a particularly unusual enzyme because it can cut a protein chain inside a membrane.