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  3. The bacterial magnesium transporter MgtA reveals highly selective interaction with specific cardiolipin species

The bacterial magnesium transporter MgtA reveals highly selective interaction with specific cardiolipin species

  • Biochim Biophys Acta Mol Cell Res. 2024 Jan;1871(1):119614. doi: 10.1016/j.bbamcr.2023.119614.
Julia Weikum 1,  Jeroen F van Dyck 2,  Saranya Subramani 3,  David P Klebl 4,  Merete Storflor 5,  Stephen P Muench 4,  Sören Abel 5,  Frank Sobott 6,  J Preben Morth 7
Affiliations

Affiliations

  • 1 Membrane Transport Group, Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, P.O. Box 1137, Blindern, 0318 Oslo, Norway; Enzyme and Protein Chemistry, Section for Protein Chemistry and Enzyme Technology, Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, 2800 Kgs. Lyngby, Denmark.
  • 2 Department of Chemistry, University of Antwerp, Campus Groenenborger, Groenenborgerlaan 171, G.V. 418, 2020 Antwerpen, Belgium.
  • 3 Membrane Transport Group, Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, P.O. Box 1137, Blindern, 0318 Oslo, Norway.
  • 4 School of Biomedical Sciences & The Astbury Centre for Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, United Kingdom.
  • 5 Infections Biology Lab, Department of Pharmacy, UiT-The Arctic University of Norway, 9037 Tromsø, Norway.
  • 6 Department of Chemistry, University of Antwerp, Campus Groenenborger, Groenenborgerlaan 171, G.V. 418, 2020 Antwerpen, Belgium; School of Molecular and Cellular Biology & The Astbury Centre for Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, United Kingdom. Electronic address: [email protected].
  • 7 Membrane Transport Group, Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, P.O. Box 1137, Blindern, 0318 Oslo, Norway; Enzyme and Protein Chemistry, Section for Protein Chemistry and Enzyme Technology, Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, 2800 Kgs. Lyngby, Denmark; Institute for Experimental Medical Research (IEMR), Oslo University Hospital, Ullevål PB 4956 Nydalen, NO-0424 Oslo, Norway. Electronic address: [email protected].
PMID: 37879515 DOI: 10.1016/j.bbamcr.2023.119614
Abstract

The Bacterial magnesium transporter A (MgtA) is a specialized P-type ATPase important for Mg2+ import into the cytoplasm; disrupted magnesium homeostasis is linked to intrinsic ribosome instability and Antibacterial resistance in Salmonella strains. Here, we show that MgtA has functional specificity for cardiolipin 18:1. Still, it reaches maximum activity only in combination with cardiolipin 16:0, equivalent to the major components of native cardiolipin found in E. coli membranes. Native mass spectrometry indicates the presence of two binding sites for cardiolipin, agreeing with the kinetic studies revealing that a cooperative relationship likely exists between the two cardiolipin variants. This is the first experimental evidence of cooperative effects between lipids of the same class, with only minor variations in their acyl chain composition, acting on a membrane protein. In summary, our results reveal that MgtA exhibits a highly complex interaction with one cardiolipin 18:1 and one cardiolipin 16:0, affecting protein activity and stability, contributing to our understanding of the particular interactions between lipid environment and membrane proteins. Further, a better understanding of Mg2+ homeostasis in bacteria, due to its role as a virulence regulator, will provide further insights into the regulation and mechanism of Bacterial infections.

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