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. 2017 Apr 12;3(4):e1602794. doi: 10.1126/sciadv.1602794

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Copyright © 2017, The Authors

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

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Fig. 1 — The ligand-binding N-terminal extracellular domain includes the repeat EGF domain followed by three Lin-12/Notch repeats (LNR) and the heterodimerization domain (HD). The LNR segments and the HD comprise the NRR. The transmembrane segment follows. The cytosolic domain contains the RAM domain, followed by ankyrin (ANK) repeats, the transcriptional activation domain (TAD), and the C-terminal terminal proline-, glutamic acid–, serine-, and threonine-rich (PEST) domain. The construct used in this study (the Notch-TMD) is the transmembrane segment plus the immediate juxtamembrane regions, highlighted on the right. Major γ-secretase cut sites are labeled red. The S2 metalloprotease cut site precedes Val¹⁷²¹.