Unconventional transport of metal ions and protons by Nramps

Abstract

Rudnick highlights a kinetic analysis of a bacterial Nramp transporter that focuses on how H⁺ gradients are coupled to metal transport.

Figure 1.

A canonical mechanism for metal-proton symport. In a conventional transport mechanism, metal and protons bind to central binding sites in the transporter in an outward-facing conformation. In APC/FIRL transporters, binding sites are found near the interface between the scaffold (blue) and bundle (orange) domains. After binding metal (green) and proton(s) (red) to the outward-facing transporter (top), reorganization of the bundle domain (right) closes the extracellular pathway and opens a pathway between the binding sites and the cytoplasm (lower right). After release of metal and proton(s) to the cytoplasm (bottom), the bundle domain isomerizes (left), returning to the outward-facing conformation (top left).

Figure 2.

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.