Structural studies of human y-secretase
Human gamma-secretase is a large membrane protein complex catalyzing a novel reaction of intramembrane proteolysis. This activity is important in a number of cellular signaling pathways. There are three known gamma-secretase components, presenilin, nicastrin and beta-catenin. Mutations in presenilin cause familial and early-onset Alzheimer's disease. We propose structural studies of the complex of these protein components aiming at understanding the mechanism of intramembrane proteolysis and the effects of mutations that cause the disease.