Structural and functional properties of a plant NRAMP-related aluminum transporter

The transport of transition metal ions by members of the SLC11/NRAMP family constitutes a ubiquitous mechanism for the uptake of Fe$^{2+}$ and Mn$^{2+}$ across all kingdoms of life. Despite the strong conservation of the family, two of its branches have evolved a distinct substrate preference with one mediating Mg$^{2+}$ uptake in prokaryotes and another the transport of Al$^{3+}$ into plant cells. Our previous work on the SLC11 transporter from Eggerthella lenta revealed the basis for its Mg$^{2+}$ selectivity (Ramanadane et al., 2022). Here, we have addressed the structural and functional properties of a putative Al$^{3+}$ transporter from Setaria italica. We show that the protein transports diverse divalent metal ions and binds the trivalent ions Al$^{3+}$ and Ga$^{3+}$, which are both presumable substrates. Its cryo-electron microscopy (cryo-EM) structure displays an occluded conformation that is closer to an inward- than an outward-facing state, with a binding site that is remodeled to accommodate the increased charge density of its transported substrate.