Fig. 5 |. Model of AE1-mediated bicarbonate transport and diverse mechanisms of AE1 transport inhibition by pharmacologically different drugs.

a, Overlay of membrane domains of human AE1 and AtBor1 from A. thaliana (purple) showing similar gate conformations, while the core domains appear in different states. Cytoplasmic view of the overlay reveals a channel in AtBor1 that overlaps with the putative anion exit channel in AE1 ending near R694, and connecting the AE1 bicarbonate binding site and the cytosol. b, Overlay of AE1 and AtBor1 anion binding sites suggests an elevator mechanism where the core domain moves towards the cytoplasmic site (black arrows) and TM10 kinks away from the gate domain (black arrow) to release substrates towards the cytoplasm (dashed arrows). c, Schematic illustrating AE1-mediated bicarbonate (orange) transport, as well as pharmacological differences between the inhibitors DIDS/H₂DIDS, dipyridamole and niflumic acid (magenta). Note, all tested inhibitors prevent translocation-related relative movements of gate and core domains, which are shown in dark blue and pale cyan, respectively.