Figure 6: Proposed model for the ion-conduction mechanism of MgtE.

(a) Model for the Mg²⁺ transport mechanism. A schematic representation of MgtE, viewed from the plane in the membrane, is shown. The Mg²⁺ binding to the cytosolic domain stabilizes the MgtE in the closed state (left panel), while the M2 and M3 sites do not bind to Mg²⁺, and thus the periplasmic Mg²⁺ does not affect the gating of MgtE. After the dissociation of Mg²⁺ from the cytosolic domain, MgtE adopts the open form (right panel). In the open form, the electrostatic interaction between Asp432 and Mg²⁺, and the hydrogen bonds between Asp432 and the Mg²⁺ hydration shells enable the precise recognition and high-speed conduction of Mg²⁺. (b) Model for the Ca²⁺ conduction mechanism. Solid and dashed lines represent the major and minor ion pathways for Ca²⁺, respectively. Although periplasmic Ca²⁺ can interact with the M3 site, its weak affinity does not stabilize MgtE in the closed form (left panel). In the open form (right panel), Ca²⁺ cannot pass through the selectivity filter (that is, Asp432) efficiently, because the interaction between Asp432 and its hydration shell is not optimal. The interaction between the M3 site and Ca²⁺ also contributes to the slowing of its transport rate. The major portion of Ca²⁺ diffuses back to the periplasmic side through the hydrophobic gate, while a small portion overcomes the barrier in the selectivity filter, which results in the weak Ca²⁺ transport activity of MgtE. (c) Gating model of the ion-conducting pore by the periplasmic gating sites. A schematic representation of MgtE, viewed from the periplasmic side, is shown. Periplasmic Mn²⁺ binds to the M2, M2′ and M3 sites with high affinity, which fixes MgtE in the closed form. This results in the high selectivity for Mg²⁺ over Mn²⁺.