Transport by a mixed mechanism with a proton channel. In a mixed mechanism, metal (green) is transported by protein conformational changes as in the canonical mechanism (Fig. 1), but protons (red) can cross the membrane through a channel in the scaffold domain (blue). This mechanism could involve protonation of a residue in the binding site that coordinates the metal ion so that binding of the metal (top center) would displace the proton, injecting it into the channel (top right). Dissociation of the proton from the channel into the cytoplasm (bottom center) could be a difficult-to-reverse step, thereby minimizing the reverse reaction. How the transporter couples dissociation of protons and metal ions to the cytoplasm is unclear at present.