A repulsion mechanism explains magnesium permeation and selectivity in CorA

Magnesium (Mg2+) plays a central role in biology, regulating the activity of many enzymes and stabilizing the structure of key macromolecules. In bacteria, CorA is the primary source of Mg2+ uptake and is self-regulated by intracellular Mg2+. Using a gating mutant at the divalent ion binding site, we were able to characterize CorA selectivity and permeation properties to both monovalent and divalent cations under perfused two-electrode voltage clamp. The present data demonstrate that under physiological conditions, CorA is a multioccupancy Mg2+-selective channel, fully excluding monovalent cations, and Ca2+, whereas in absence of Mg2+, CorA is essentially nonselective, displaying only mild preference against other divalents (Ca2+ > Mn2+ > Co2+ > Mg2+ > Ni2+). Selectivity against monovalent cations takes place via Mg2+ binding at a high-affinity site, formed by the Gly-Met-Asn signature sequence (Gly312 and Asn314) at the extracellular side of the pore. This mechanism is reminiscent of repulsion models proposed for Ca2+ channel selectivity despite differences in sequence and overall structure.