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Regions of the flippase Dnf1 called transmembrane segments 3–4 (TM3-4) are responsible for phospholipid selection. We propose that the phospholipid headgroup is selected and transported along a groove between TM1, 3, and 4, allowing the hydrophobic lipid tail to simply reorient in the hydrophobic core of the membrane bilayer. TM3-4 is highlighted in purple within this homology model of the Dnf1 structure.
