[HTML][HTML] γ-Secretase, evidence for multiple proteolytic activities and influence of membrane positioning of substrate on generation of amyloid β peptides of varying …

MP Murphy, LJ Hickman, CB Eckman, SN Uljon… - Journal of Biological …, 1999 - ASBMB
γ-Secretase activity is the final cleavage event that releases the amyloid β peptide (Aβ) from
the β-secretase cleaved carboxyl-terminal fragment of the amyloid β protein precursor
(APP). No protease responsible for this highly unusual, purportedly intramembranous,
cleavage has been definitively identified. We examined the substrate specificity of γ-
secretase by mutating various residues within or adjacent to the transmembrane domain of
the APP and then analyzing Aβ production from cells transfected with these mutant APPs by …