Evidence for phospholipid export from the bacterial inner membrane by the Mla ABC transport system

Nat Microbiol. 2019 Oct;4(10):1692-1705. doi: 10.1038/s41564-019-0481-y. Epub 2019 Jun 24.


The Mla pathway is believed to be involved in maintaining the asymmetrical Gram-negative outer membrane via retrograde phospholipid transport. The pathway is composed of three components: the outer membrane MlaA-OmpC/F complex, a soluble periplasmic protein, MlaC, and the inner membrane ATPase, MlaFEDB complex. Here, we solve the crystal structure of MlaC in its phospholipid-free closed apo conformation, revealing a pivoting β-sheet mechanism that functions to open and close the phospholipid-binding pocket. Using the apo form of MlaC, we provide evidence that the inner-membrane MlaFEDB machinery exports phospholipids to MlaC in the periplasm. Furthermore, we confirm that the phospholipid export process occurs through the MlaD component of the MlaFEDB complex and that this process is independent of ATP. Our data provide evidence of an apparatus for lipid export away from the inner membrane and suggest that the Mla pathway may have a role in anterograde phospholipid transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Biological Transport
  • Cell Membrane / metabolism*
  • Crystallography, X-Ray
  • Gram-Negative Bacteria / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / metabolism
  • Models, Biological
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Periplasm / metabolism
  • Phospholipids / metabolism*
  • Protein Binding
  • Protein Conformation, beta-Strand


  • ATP-Binding Cassette Transporters
  • Bacterial Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • Multiprotein Complexes
  • Phospholipids