title: The magnesium transporter A is activated by cardiolipin and is highly sensitive to free magnesium in vitro.
abstract: The magnesium transporter A (MgtA) is a specialized P-type ATPase, believed to import Mg(2+) into the cytoplasm. In Salmonella typhimurium and Escherichia coli, the virulence determining two-component system PhoQ/PhoP regulates the transcription of mgtA gene by sensing Mg(2+) concentrations in the periplasm. However, the factors that affect MgtA function are not known. This study demonstrates, for the first time, that MgtA is highly dependent on anionic phospholipids and in particular, cardiolipin. Colocalization studies confirm that MgtA is found in the cardiolipin lipid domains in the membrane. The head group of cardiolipin plays major role in activation of MgtA suggesting that cardiolipin may act as a Mg(2+) chaperone for MgtA. We further show that MgtA is highly sensitive to free Mg(2+) (Mg(2+)free) levels in the solution. MgtA is activated when the Mg(2+)free concentration is reduced below 10 μM and is strongly inhibited above 1 mM, indicating that Mg(2+)free acts as product inhibitor. Combined, our findings conclude that MgtA may act as a sensor as well as a transporter of Mg(2+).
authors.affiliation: Norwegian Centre of Molecular Medicine, Nordic EMBL Partnership University of Oslo, Oslo, Norway.
authors.forename: Saranya
authors.initials: S
authors.lastname: Subramani
authors.affiliation: Norwegian Centre of Molecular Medicine, Nordic EMBL Partnership University of Oslo, Oslo, Norway.|Institute for Experimental Medical Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Harmonie
authors.initials: H
authors.lastname: Perdreau-Dahl
authors.affiliation: Norwegian Centre of Molecular Medicine, Nordic EMBL Partnership University of Oslo, Oslo, Norway.|Institute for Experimental Medical Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Jens Preben
authors.identifier: http://orcid.org/0000-0003-4077-0192
authors.initials: JP
authors.lastname: Morth
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D002308:Cardiolipins / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry; D004926:Escherichia coli / Q000201:enzymology* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*
chemical_list: D002308:Cardiolipins; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D000251:Adenosine Triphosphatases; C490561:MgtA protein, E coli; D008274:Magnesium
keywords: ATPase assay; E. coli; MgtA; P-type ATPase; biochemistry; biophysics; cardiolipin; magnesium inhibition; magnesium transport; structural biology