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. 2018 Jul 2;150(7):933–947. doi: 10.1085/jgp.201711957

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© 2018 Falzone et al.

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Figure 5. — Structural differences between the TMME16 ion and lipid pores. (A) Structural alignment of nhTMEM16 (gray) and TMEM16A (pink) pathways. (B) Credit card model of lipid scrambling. (C) Alignment of the permeation pathways of the high-resolution structures of nhTMEM16 and TMEM16A highlighting the different tilts of TM4. The TM3 and TM5 from each structure are shown as gray ribbons, TM6 are shown as black ribbons, and TM4 are shown in color. Colors of TM4 are as follows: nhTMEM16 is red, mTMEM16A +Ca²⁺ is orange, mTMEM16A −Ca²⁺ is yellow, mTMEM16A in nanodiscs is green, and mTMEM16A in Lauryl Maltose Neopentyl Glycol is blue. (D) Cartoon depicting the ‘dynamic switch’ model for the dual-function activity of the TMEM16 scramblases. See text for details.