Benedikt Kretner, Akio Fukumori, Peer-Hendrik Kuhn, Blanca Isabel Pérez-Revuelta, Stefan F. Lichtenthaler, Christian Haass and Harald Steiner Important functional role of residue x of the presenilin GxGD protease active site motif for APP substrate cleavage specificity and substrate selectivity of γ-secretase Journal of Neurochemistry 125
γ-Secretase substrate recognition and cleavage is an incompletely understood process. Here, we show that residue x of the GxGD active site motif of γ-secretase (L383 in presenilin 1), while representing its functionally least critical residue, contributes to substrate cleavage efficiency and selectivity. Our data substantiate the critical role of the GxGD motif in the catalytic subunit of γ-secretase for substrate selection and/or cleavage efficiency.
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