Fig. 6: Ion-binding site and C-terminal domain of the NHE9*CC.

a left: cartoon representation of the NHE9 ion-binding site, located in the 6-TM core transporter domain, which is made up of two broken helices. The sodium ion (yellow sphere) is located and coordinated at the ion-binding site. right: ion-binding residues of the NHE9*CC structure are shown as blue sticks and labelled, with the identical residues of NHE9* shown as yellow sticks (PDB id: 6Z3Y). b Ion-binding residues of NHE9*CC are shown as blue sticks and NHE1 residues shown as grey sticks with Val237 and Asn266 labelled. c Hydrogen-bonding between T214-N243 and salt-bridge interaction between E239-R408 in the NHE9*CC structure are illustrated by dashed lines and the cryo-EM maps shown as grey mesh. d Top view showing how the CTD helix is positioned on the outside of the mobile TM7 linker domain. e Numerous contacts are formed between the CTD and the linker helix TM7, in particular via K301 (blue-sticks) in TM7 to residues in the CTD helix (salmon sticks and labelled). f In the NHE9* CC structure the CTD stays connected to the linker helix TM7 (protein shown as surface). g CHP1 (green, surface) binding to the CTD of NHE1 (grey, surface) moves it away from the linker helix TM7. h Alfafold2 model of NHE1 and CTD interaction to TM7 predicted as was observed in the NHE9* CC cryo-EM structure.