- Secretase
Secretases are
enzymes that "snip" pieces off a longerprotein that is embedded in thecell membrane . closer to the cell surface than BACE. The non-pathogenic middle fragment formed by an α/γ cleavage sequence is called P3.tructure
The structure of the three secretases varies widely.
* The α-secretase
gene has not been conclusively identified but is believed to be ametalloproteinase .* BACE is a transmembrane protein with an extracellular
aspartic acid protease domain.* γ-secretase is actually a
protein complex containingpresenilin ,nicastrin ,ACH-1 , andPEN-2 . Presenilin is believed to harbor the protease domain and represents an important example of an uncommon type ofprotease that cleaves targets within the cell membrane.Function
Besides their involvement in the pathogenesis of Alzheimer's, these proteins also have other functional roles in the cell.
γ-secretase plays a critical role in developmental signalling by the
transmembrane receptor Notch, freeing thecytoplasmic tail of Notch to travel to thecell nucleus to act as atranscription factor .Although BACE cleaves the extracellular domains of several transmembrane proteins, its physiological function remains unknown.
External links
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