repulsion mechanism explains magnesium permeation and selectivity in CorA

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 8; pp. 3002 - 3007
• Main Authors: Dalmas, Olivier, Sandtner, Walter, Medovoy, David, Frezza, Ludivine, Bezanilla, Francisco, Perozo, Eduardo
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 25.02.2014; National Acad Sciences
• Subjects: Amino Acid Sequence; Animals; Bacteria; Bacterial Proteins - metabolism; Binding sites; Biological Sciences; Biology; Cation Transport Proteins - metabolism; Cell Membrane Permeability - physiology; Cloning, Molecular; Cobalt; Computational Biology; Divalent cations; DNA Primers - genetics; Electric current; Electric potential; Enzymes; Genetic Vectors; Ion channels; Ions; Magnesium; Magnesium - metabolism; Models, Molecular; Molecular Sequence Data; Oocytes; Oocytes - metabolism; Patch-Clamp Techniques; Permeability; Physiology; Sequence Alignment; Signatures; Static Electricity; Thermotoga maritima - chemistry; Thermotoga maritima - genetics; Thermotoga maritima - metabolism; Xenopus laevis; electrophysiology; AMFE; Mg2+ selectivity; ion channels
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1319054111

Magnesium (Mg ²⁺) 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 Mg ²⁺ uptake and is self-regulated by intracellular Mg ²⁺. 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 Mg ²⁺-selective channel, fully excluding monovalent cations, and Ca ²⁺, whereas in absence of Mg ²⁺, CorA is essentially nonselective, displaying only mild preference against other divalents (Ca ²⁺ > Mn ²⁺ > Co ²⁺ > Mg ²⁺ > Ni ²⁺). Selectivity against monovalent cations takes place via Mg ²⁺ 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 Ca ²⁺ channel selectivity despite differences in sequence and overall structure.