The MgtE Mg²⁺ Transporter

The MgtE class of Mg²⁺ ion transporter is widespread in the bacteria, with over 50% of current genomic sequences and most marine metagenome sequences exhibiting a homolog. MgtE is the primary provider of cytosolic Mg²⁺ in those organisms that carry it. MgtE homologs are widespread in the metazoa and fungi (SLC41 family) but apparently absent in the plants. In bacteria, MgtE functions as a Mg²⁺ influx system, while in eukaryotes specific MgtE proteins may function as either influx or efflux systems. Despite their ubiquity, virtually nothing is known about the physiological role of MgtE. Bacterial MgtE proteins are homodimers, with the entire soluble domain at the N terminus and the entire membrane domain at the C terminus. A recent crystal structure of Thermus thermophilus MgtE putatively in the closed form shows that the membrane domain consists of 5 transmembrane helices, each at a substantial angle to the plane of the membrane, giving 10 transmembrane helices in the dimer. The pore is formed primarily by transmembrane segments 2 and 5. Each membrane domain is connected to the soluble domain by a single -helix orthogonal to the membrane. Attached to this ‘connecting helix’ is a soluble domain containing a superhelical bundle of 10 -helices (‘N domain’) followed by duplicated tandem cystathionine -synthase-like motifs, which end in the ‘connecting helix.’ The N domain has structural homology to the FliG protein of the flagellar motor. It is not clear how Mg²⁺ is recognized and selected. The crystal structure also contains several sites for bound Mg²⁺ ions, one within the pore. Two Mg²⁺ sites per monomer connect the ‘connecting helice’ and CBS domain to the membrane domain, while two additional sites per monomer connect the CBS- and N domains. The structure of the soluble domain with and without Mg²⁺ has also been solved. The absence of Mg²⁺ does not alter the structure of the N domain significantly, but the structure of the tandem cystathionine -synthase domains within each monomer does change to some extent. The largest change due to the absence of Mg²⁺ is that the entire cystathionine -synthase domain rotates and slightly twists 120° from the N domain. It is not clear if this rotation is part of the mechanism by which the pore opens and closes. Presumably, the bound Mg²⁺ ions in the soluble domain play a role in sensing Mg²⁺, and their dissociation could allow domain movement and lead to opening of the pore.

Graphical Abstract

3D Structure

3D Structure A ribbon representation of a side view of homodimeric MgtE from Thermus thermophilus in the plane of the membrane is shown (PDB code 2YVX).⁶ The membrane domain is colored in dark blue, the ‘connecting helices’ in light blue, the CBS domains in beige, and the N domains in red. Bound Mg²⁺ ions are shown as spheres (see text for discussion). Mg1 within the TM domain is wheat-colored, Mg2 and Mg3 are shown in gray, and Mg4 and Mg5 are shown in purple. This and similar following figures were drawn using PyMOL 1.1.¹⁸

Keywords: magnesium; MgtE; transport; homodimer; bacteria; SLC41