Figure 6.

Conformational changes in TMD4 are associated with γ-secretase complex assembly. A, Schematic diagram of Pen-2 and His-Xpress-PS1 used in this study. Positions of I213 and L383 were shown as red circles. B, Cross-linking experiments of double-Cys mt PS1 with I213C and L383C mutations, in P2KO cells with or without Pen-2 overexpression. Western blotting was performed using the anti-Xpress antibody. His-Xpress-PS1 NTF (asterisk) appeared only in the Pen-2-expressing cells. His-Xpress-PS1 holoprotein, NTFs and cross-linked products (NTF–CTF heterodimers) are shown by black arrow, asterisk, and arrowhead, respectively. Note that the cross-linked product also appeared only in the Pen-2-expressing cells.