The transport of transition metal ions by members of the SLC11/NRAMP family constitutes a ubiquitous mechanism for the uptake of Fe2+ and Mn2+ 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 Mg2+ uptake in prokaryotes and another the transport of Al3+ into plant cells. Our previous work on the SLC11 transporter from Eggerthella lenta revealed the basis for its Mg2+ selectivity (Ramanadane et al., 2022). Here, we have addressed the structural and functional properties of a putative Al3+ transporter from Setaria italica. We show that the protein transports diverse divalent metal ions and binds the trivalent ions Al3+ and Ga3+, 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.

No abstract

The transport of transition metal ions by members of the SLC11/NRAMP family constitutes a ubiquitous mechanism for the uptake of Fe2+and Mn2+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 Mg2+uptake in prokaryotes and another the transport of Al3+into plant cells. Our previous work on the SLC11 transporter fromEggerthella lentarevealed the basis for its Mg2+selectivity (Ramanadane et al., 2022). Here we have addressed the structural and functional properties of a putative Al3+transporter fromSetaria italica. We show that the protein transports diverse divalent metal ions and binds the trivalent ions Al3+and Ga3+, which are both presumable substrates. Its 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.