Divalent cation (Mg²⁺, Co²⁺ and Ni²⁺) transport system, CorA.  Helical tilting and rotation in TM1 generates an iris-like motion that increases the diameter of the permeation pathway, triggering ion conduction, thus defining the gating mechanism (Dalmas et al. 2014).

Bacteria

CorA of E. coli (P0ABI4)

Divalent cation (Mg²⁺, Co²⁺ and Ni²⁺) transport system, CorA

Bacteria

CorA of Salmonella typhimurium (P0A2R8)

Magnesium transport protein CorA

Bacteria

CorA of Bacillus subtilis

Aluminum resistance protein Al^R1p; Alr1; ALR1, LLR1; MNR1 (Mg²⁺ homeostasis transporter [Mg²⁺ regulated]) Al^R1p and Al^R2p (P43553; a close paralogue) both catalyze uptake of Mg²⁺ and a variety of heavy metals (da Costa et al., 2007). Truncation of Alr1 showed that the N-terminal 239 amino acids and the C-terminal 53 amino acids are not essential for magnesium uptake (Lee and Gardner 2006). Mutations in the C-terminal part of ALR1 that is homologous to bacterial CorA magnesium transporters that gave severe phenotypes had amino acid changes in the small region containing the TMSs. Eighteen single amino acid mutants in this region were classified into three categories for magnesium uptake: no, low and moderate activity. Conservative mutations that reduced or inactivated uptake led to the identification of Ser(729), Ile(746) and Met(762) (part of the conserved GMN motif) as critical residues. High expression of inactive mutants inhibited the capability of wild-type Alr1 to transport magnesium, consistent with Alr1 forming homo-oligomers (Lee and Gardner 2006). Alr1 may play a role in cadmium resistance (Kern et al. 2005).

Yeast

Al1^Rp of Saccharomyces cerevisiae

Inner mitochondrial membrane manganese channel protein Mn^R2p or MRS2-11.  The regulatory domain of  Mrs2 from the yeast inner mitochondrial membrane is similar to the E. coli regulatory domain of CorA with Met309 serving the same function as Met291 in CorA (Khan et al. 2013).

Yeast

Mn^R2p of Saccharomyces cerevisiae

Putative metal ion transporter C27B12.12c

C27B12.12c of Schizosaccharomyces pombe

Divalent metal ion (Mg²⁺, Ca²⁺, Ni²⁺, etc.) transporter of 317 aas and 3 TMSs.  The cryo-EM structure shows a pentameric channel with an asymmetric domain structure and featuring differential separations between the trans-segments, probably reflecting mechanical coupling of the cytoplasmic domain to the transmembrane domain and suggesting a gating mechanism (Cleverley et al. 2015).

Archaea

CorA of Methanocaldococcus jannaschii (Methanococcus jannaschii)

Magnesium transport protein, CorA.  The structure at 2.7 Å resolution is known. The CorA monomer has a C-terminal membrane domain containing two transmembrane segments and a large N-terminal cytoplasmic soluble domain. In the membrane, CorA forms a homopentamer shaped like a funnel which binds fully hydrated Mg²⁺ in the periplasm (Maguire 2006). A ring of positive charges are external to the ion-conduction pathway at the cytosolic membrane interface, and highly negatively charged helices in the cytosolic domain  appear to interact with the ring of positive charge to facilitate Mg²⁺ entry. Mg²⁺ ions are present in the cytosolic domain that are well placed to control the interaction of the ring of positive charge and the negatively charged helices, and thus, control Mg²⁺ entry (Maguire 2006).  Gating is achieved by helical rotation upon the binding of a metal ion substrate to the regulatory binding sites. The preference for Co²⁺ over Mg²⁺ has been reported to be determined by the presence of threonine side chains in the channel (Nordin et al. 2013), but more recently, Kowatz and Maguire 2018 showed that Co²⁺ is not a substrate, and that the intersubunit bound Mg²⁺ is not required for function and does not control the open versus closed states.

Bacteria

CorA of Thermotoga maritima

YfjQ of Bacillus subtilis

Putative CorA protein of 302 aas

Firmictues

CorA of Streptococcus sanguinis

MIP family protein of 366 aas. Mg²⁺,Co²⁺ and the CorA-specific inhibitor (Co(III) hexamine chloride) bind in the loop at the same binding site. This site includes the glutamic acid residue from the conserved "MPEL" motif (Hu et al. 2009).

Actinobacteria

CorA of Mycobacterium tuberculosis

The CorA-homologous magnesium ion transporter of 831 aas, Mgt1.  Is critical for parasite development and virulence (Zhu et al. 2009).

Euglenozoa

Mgt1 of Leishmania major

Putative Mg²⁺ transporter of 322 aas and 2 or 3 TMSs.

CorA protein of Lactobacillus phage LfeInf

Uncharacterized CorA homologue of 373 aas and 3 TMSs (Pohland and Schneider 2019).

CorA of Acaryochloris marina

Zn²⁺/Cd²⁺ efflux system, ZntB. Mg²⁺ is not transported. Wan et al. 2011 reported crystal structures in dimeric and physiologically relevant homopentameric forms at 2.3 Å and 3.1 Å resolutions, respectively. The funnel-like structure is similar to that of the homologous Thermotoga maritima CorA Mg²⁺ channel and a Vibrio parahaemolyticus ZntB (VpZntB). However, the central α7 helix forming the inner wall of the StZntB funnel is oriented perpendicular to the membrane instead of the marked angle seen in CorA or VpZntB. Consequently, the StZntB funnel pore is cylindrical, not tapered, which may represent an "open" form of the ZntB soluble domain. There are three Zn²⁺ binding sites in the full-length ZntB, two of which could be involved in Zn²⁺ transport.

Bacteria

ZntB of Salmonella enterica serovar Typhimurium

The ZntB Zn²⁺/Cd²⁺ transporter. The 1.9Å structure of the N-terminal cytoplasmic domain of ZntB has been solved (Tan et al., 2009).

Bacteria

ZntB of Vibrio parahaemolyticus (Q87M69)

Mitochondrial inner membrane Mg²⁺ channel protein, Mrs2 (Schindl et al., 2007).  Mutational analyses have been carried out, suggesting that internal Mg²⁺ affects intron splicing (Weghuber et al. 2006). MRS2 is involved in mitochondrial Mg²⁺ homeostasis (Schäffers et al. 2018). The G-M-N motif determines the ion selectivity, likely together with the negatively charged loop at the entrance of the channel, thereby forming the Mrs2p selectivity filter (Sponder et al. 2013).

Yeast, plant & animals

Mrs2 of Saccharomyces cerevisiae (Q01926)

Mg²⁺ transporter, MIT3, of 478 aas with 2 C-terminal TMSs (Wunderlich 2022)

MIT3 of Plasmodium falciparum

Magnesium transporter 9, Mgt9, of 378 aas and possibly 2 TMSs, one at residue 160 and one C-terminal. In cassava (Manihot esculenta) This protein associates with aquaporin PIP2;7 (B2M0U5) interact synergistically to promote water and Mg2+ uptake (Ma et al. 2023).

Mgt9 of Arabidopsis thaliana

High affinity root Mg²⁺ transporter, Mrs2/MGT1/MRS2-10.  Plants have at least  11 Mrs2 homologues, and they can form homo as well as heterooligomeric channels (Schmitz et al. 2013). Expression in an E. coli triple mutant, corA mgtA yhiD, which required high (>10 mM) Mg²⁺ for growth, allowed growth on >1 mM Mg²⁺ and resulted in Al³⁺ sensitivity (Ishijima et al. . 2015). It therefore appears that MRS2-10 catalyzes Mg²⁺ and Al ³⁺ uptake.

Plants

Mrs2-10 of Arabidposis thaliana (Q9SAH0)

Magnesium transporter MRS2-11, MRS2B, chloroplastic (Magnesium Transporter 10) (AtMGT10).  Expression in an E. coli triple mutant, corA mgtA yhiD, which required high (>10 mM) Mg²⁺ for growth, allowed growth on >1 mM Mg²⁺ and resulted in Al³⁺ sensitivity (Ishijima et al. 2015).

Plants

MGT10 of Arabidopsis thaliana

Mitochondrial inner membrane magnesium transporter MFM1; LPE10 (MRS2 function modulating factor 1)

MRS2 (HPTm MRS2L) of 443 aas and 2 C-terminal TMSs. Implicated in mitochondrial Mg²⁺ homeostasis (Schäffers et al. 2018). The human MRS2 magnesium-binding domain is a regulatory feedback switch for channel activity (Uthayabalan et al. 2023). It is a magnesium (Mg²⁺) entry protein channel in mitochondria. Whereas MRS2 contains two transmembrane domains constituting a pore in the inner mitochondrial membrane, most of the protein resides within the matrix. This research exposes a mechanism for human MRS2 autoregulation by negative feedback from the NTD and identifies a novel gain of function mutant (Uthayabalan et al. 2023).

MRS2 of Homo sapiens

MIT1 of 529 aas and 2 C-terminal TMSs. It is a Mg²⁺/Co²⁺/Ni²⁺ ion channel (Wunderlich 2022).

MIT1 of Plasmodium falciparum

Magnesium transport channel, MIT2, of 468 aas with 2 C-terminal TMSs.

MIT2 of Plasmodium falciparum