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The lack of detailed information on the interactions between substrates and enzymes is a major gap in understanding the mechanisms of many proteases. Using the Alzheimer’s disease protease γ-secretase as an example, we show how a previously developed versatile chemical biology approach allows to systematically identify molecular interactions with the enzyme at the amino acid level of the substrate...
Intramembrane proteolysis has emerged as a key mechanism required for membrane proteostasis and cellular signaling. One of the intramembrane-cleaving proteases (I-CLiPs), γ-secretase, is also intimately implicated in Alzheimer’s disease, a major neurodegenerative disease and leading cause of dementia. High-resolution crystal structural analyses have revealed that I-CLiPs harbor their active sites...
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