Pore-forming scissors? A first structural glimpse of gamma-secretase
Harald Steiner1, Manuel Than, Wolfram Bode
1Adolf-Butenandt-Institute, Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Ludwig-Maximilians University, Schillerstrasse 44, 80336 Munich, Germany. harald.steiner@med.uni-muenchen.de
Abstract:
Amyloid plaques, which are composed of amyloid-beta peptide (Abeta), signify Alzheimer's disease pathology. Secretases generate Abeta by processing the beta-amyloid precursor protein. gamma-Secretase, a complex comprising four different proteins, liberates Abeta from its precursor by intramembrane proteolysis. The first impression of the shape of gamma-secretase has recently been revealed by electron microscopy. It indicates a spherical transmembrane particle with an interior chamber that, presumably, accommodates its catalytic residues, and two openings that might be exit sites for the cleavage products.
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