Figure 4. Glycans and sequence diversity concentrate around the membrane distal head of the transferrin receptor.

a. The structure of the transferrin receptor is shown as a grey surface with variable residues coloured in yellow (Shannon sequence entropy 0.3-0.5), orange (0.5-0.8) and red (>0.8). Modelled glycans are shown in green and transferrin as a red cartoon. b. The structure of the trypanosome transferrin receptor heterodimer (ESAG6 in dark blue and ESAG7 in light blue) bound to human transferrin (red) with N-linked glycans modelled in green. c. Views of the membrane distal surface of the transferrin receptor. In the left-hand panel, ESAG6 is shown as a dark blue surface and ESAG7 as a light blue surface. The modelled glycans are in green. The middle panel is coloured as b. In the right-hand panel, the transferrin receptor is shown as a grey surface with residues which directly contact transferrin in red. Human transferrin receptor is shown as a transparent cartoon in red. d. A static comparison of free and transferrin bound transferrin receptors with the N-terminal domains of variant surface glycoproteins in grey. This shows the green glycans to provide sufficient space in the VSG layer to provide access for transferrin. The VSG molecules will also be glycosylated, at positions which differ depending on the VSG variant (not shown). The springs represent that these molecules also have regions not modelled and their relative positions within the dynamic trypanosome surface will vary.