Structural and Mechanistic Basis of Proton-Coupled Metal Ion Transport in the SLC11/NRAMP Family

Abstract

Secondary active transporters of the SLC11/NRAMP family catalyse the uptake of iron and manganese into cells. These proteins are highly conserved across all kingdoms of life and thus likely share a common transport mechanism. Here we describe the structural and functional properties of the prokaryotic SLC11 transporter EcoDMT. Its crystal structure reveals a previously unknown outward-facing state of the protein family. In proteoliposomes EcoDMT mediates proton-coupled uptake of manganese at low micromolar concentrations. Mutants of residues in the transition-metal ion-binding site severely affect transport, whereas a mutation of a conserved histidine located near this site results in metal ion transport that appears uncoupled to proton transport. Combined with previous results, our study defines the conformational changes underlying transition-metal ion transport in the SLC11 family and it provides molecular insight to its coupling to protons.

Accumulation and Enrichment of Trace Elements by Yeast Cells and Their Applications: A Critical Review

“…More trace elements enter yeast cells and stimulate them to produce more glutathione and other proteins. Activated metal protein chelates are formed when these proteins combine with metal trace elements [128]. In order to prevent the excess of metal trace elements and metal toxicity in yeast cells, it is extremely crucial to enhance the detoxification pathway of yeast and the synthesis of metal-chelating high-affinity ligands, such as glutathione pathway, metallothionein, and PC as mentioned above [63,93].…”

“…On the other hand, overexpression of CTR1 and CTR3 greatly promoted copper transport by about 10-fold [122]. SMF1 has a wide range of metal specificity and is often optimized and engineered to enhance the absorption of metals including Fe and Ni [128]. Express hyperactive Aft1 alleles Aft1-1up lead to iron cells accumulating up to four-fold more endogenous iron than Aft1-expressing cells [79].…”

Plasma-Membrane-Localized Transporter NREET1 is Responsible for Rare Earth Element Uptake in Hyperaccumulator Dicranopteris linearis

“…The natural resistance-associated macrophage proteins (NRAMP) family members are widespread in different organisms. , These proteins can transport a wide range of divalent metal substrates, and among many of them play a vital role in the Mn homeostasis in plants, such as At Nramp1– At Nramp4 in Arabidopsis thaliana − and Os Nramp3 in rice . It is noteworthy that, some NRAMP members are found to specifically transport trivalent Al, including OsNrat1 in rice and SbNrat1 in sorghum, , which play critical roles in Al uptake and detoxification in plants.…”