Catalan et al.Supplemental Material.AJP.25.pdf

AE4 is a HCO₃^- transporter that is important for electrolyte transport and pH regulation in epithelia, which has been proposed to mediate Cl^-/cation-HCO₃^- exchange. However, critical residues sustaining transport activity are not known. In this study, we show that AE4 is able to coordinate HCO₃^- and Na⁺ or K⁺ at the TM3-TM10 interface, and that residues T448 and T756 are crucial for cation binding and transport cycle.