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

Julia Weikum, Jeroen F. van Dyck, Saranya Subramani, David P. Klebl, Merete Storflor, Stephen P. Muench, Sören Abel, Frank Sobott*, J. Preben Morth*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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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.
Original languageEnglish
Article number119614
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume178
Issue number1
Number of pages15
ISSN0167-4889
DOIs
Publication statusPublished - 2024

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