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. 2016 Aug 23;2:16026. doi: 10.1038/celldisc.2016.26

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Copyright © 2016 SIBS, CAS

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A γ-secretase–APP recognition model and its validation by mutations. (a) Charge distribution of human γ-secretase (PDB code: 5A63) and the APP TM domain (PDB code: 2LP1). The two potential charge interaction areas are encircled with dashed lines. (b) Epsilon-cleavage assay cleavage efficiency of C99 proteins with mutations within the transmembrane domain (TMD) region indicates that the C-terminal region of TMD is more important than the N terminus of TMD. (c) Epsilon-cleavage assay validation of an N-terminal key residue (D7, left panel) and C-terminal key residue (K53, right panel) in C99 cleavage by γ-secretase (error bars=s.e.m., n=3, *P<0.05; **P<0.01; ***P<0.001 (versus WT)).