title: A repulsion mechanism explains magnesium permeation and selectivity in CorA.
abstract: 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.
authors: Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637.
authors: Olivier
authors: O
authors: Dalmas
authors: Walter
authors: W
authors: Sandtner
authors: David
authors: D
authors: Medovoy
authors: Ludivine
authors: L
authors: Frezza
authors: Francisco
authors: F
authors: Bezanilla
authors: Eduardo
authors: E
authors: Perozo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology*; D003001:Cloning, Molecular; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D005822:Genetic Vectors; D008274:Magnesium / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D016415:Sequence Alignment; D055672:Static Electricity; D020124:Thermotoga maritima / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D017931:DNA Primers; D008274:Magnesium
keywords: AMFE; Mg2+ selectivity; electrophysiology; ion channels