GxGD-type intramembrane cleaving proteases (I-CLiPs) form a family of proteolytic enzymes that feature an aspartate-based catalytic mechanism. Yet, they structurally and functionally largely differ from the classical pepsin-like aspartic proteases. Among them are the archaeal enzyme FlaK, processing its substrate FlaB2 during the formation of flagella and γ-secretase, which is centrally involved in the etiology of the neurodegenerative Alzheimer's disease.
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