A Monomer-Dimer Equilibrium Tunes Phospholipid Handling by Campylobacter jejuni MlaC to the Bacteriums Unique…

Abstract

The Gram-negative bacterial cell envelope features an asymmetric outer membrane, that confers intrinsic resistance to toxins. Maintenance of this barrier relies on the Mla system, which mediates retrograde transport of mislocalized phospholipids. In Escherichia coli, this system comprises the lipoprotein MlaA, the periplasmic shuttle protein MlaC, and the ABC transporter complex MlaFEDB. Intriguingly, in Campylobacter jejuni, mlaA and mlaC share an operon with an encoded Resistance-Nodulation-cell Division antiporter potentially involved in anterograde phospholipid transport.

Here, we describe the functional and mechanistical characterization of Cj MlaC. Complementation experiments in E. coli show that Cj MlaC functions independently of the native Mla system. Native mass spectrometry revealed that Cj MlaC uniquely exists as both monomer and dimer. Lipid binding stabilized the dimer and ion mobility mass spectrometry showed that conformational transitions precede phospholipid release, suggesting a cycle between a low-affinity monomer and a higher-lipid-affinity dimer. Cj MlaC binds phospholipid species distinct from Ec MlaC, showing an increased propensity for lysophospholipids, consistent with the unusually lysophospholipid-rich lipidome of C. jejuni, indicative of evolutionary adaptation to this unique lipid environment. Collectively, these findings uncover structural and mechanistic features of Cj MlaC and support divergent physiological roles for Cj and Ec MlaC in phospholipid trafficking.

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BibTeX

@misc{costa2026monomerdimer,
  title = {{A Monomer-Dimer Equilibrium Tunes Phospholipid Handling by Campylobacter jejuni MlaC to the Bacteriums Unique Lipidome}},
  author = {L. Fernandes da Costa and T. Rath and S. Spiewag and L. Leipold and C. Bonifer and N. M. Bui and M. Lazarova and W. E. Foong and H.-K. Tam and A. Herrmann and C. Glaubitz and K. M. Pos and N. Morgner},
  howpublished = {bioRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.28.747810},
  url = {https://www.biorxiv.org/content/10.64898/2026.08.28.747810v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - A Monomer-Dimer Equilibrium Tunes Phospholipid Handling by Campylobacter jejuni MlaC to the Bacteriums Unique Lipidome
AU  - L. Fernandes da Costa
AU  - T. Rath
AU  - S. Spiewag
AU  - L. Leipold
AU  - C. Bonifer
AU  - N. M. Bui
AU  - M. Lazarova
AU  - W. E. Foong
AU  - H.-K. Tam
AU  - A. Herrmann
AU  - C. Glaubitz
AU  - K. M. Pos
AU  - N. Morgner
PY  - 2026
DA  - 2026/08/28
PB  - bioRxiv
DO  - 10.64898/2026.08.28.747810
UR  - https://www.biorxiv.org/content/10.64898/2026.08.28.747810v1
AB  - The Gram-negative bacterial cell envelope features an asymmetric outer membrane, that confers intrinsic resistance to toxins. Maintenance of this barrier relies on the Mla system, which mediates retrograde transport of mislocalized phospholipids. In Escherichia coli, this system comprises the lipoprotein MlaA, the periplasmic shuttle protein MlaC, and the ABC transporter complex MlaFEDB. Intriguingly, in Campylobacter jejuni, mlaA and mlaC share an operon with an encoded Resistance-Nodulation-cell Division antiporter potentially involved in anterograde phospholipid transport.  Here, we describe the functional and mechanistical characterization of Cj MlaC. Complementation experiments in E. coli show that Cj MlaC functions independently of the native Mla system. Native mass spectrometry revealed that Cj MlaC uniquely exists as both monomer and dimer. Lipid binding stabilized the dimer and ion mobility mass spectrometry showed that conformational transitions precede phospholipid release, suggesting a cycle between a low-affinity monomer and a higher-lipid-affinity dimer. Cj MlaC binds phospholipid species distinct from Ec MlaC, showing an increased propensity for lysophospholipids, consistent with the unusually lysophospholipid-rich lipidome of C. jejuni, indicative of evolutionary adaptation to this unique lipid environment. Collectively, these findings uncover structural and mechanistic features of Cj MlaC and support divergent physiological roles for Cj and Ec MlaC in phospholipid trafficking.
ER  -

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