LptM promotes oxidative maturation of the lipopolysaccharide translocon by substrate binding mimicry

Nat Commun. 2023 Oct 11;14(1):6368. doi: 10.1038/s41467-023-42007-w.


Insertion of lipopolysaccharide (LPS) into the bacterial outer membrane (OM) is mediated by a druggable OM translocon consisting of a β-barrel membrane protein, LptD, and a lipoprotein, LptE. The β-barrel assembly machinery (BAM) assembles LptD together with LptE at the OM. In the enterobacterium Escherichia coli, formation of two native disulfide bonds in LptD controls translocon activation. Here we report the discovery of LptM (formerly YifL), a lipoprotein conserved in Enterobacteriaceae, that assembles together with LptD and LptE at the BAM complex. LptM stabilizes a conformation of LptD that can efficiently acquire native disulfide bonds, whereas its inactivation makes disulfide bond isomerization by DsbC become essential for viability. Our structural prediction and biochemical analyses indicate that LptM binds to sites in both LptD and LptE that are proposed to coordinate LPS insertion into the OM. These results suggest that, by mimicking LPS binding, LptM facilitates oxidative maturation of LptD, thereby activating the LPS translocon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Outer Membrane Proteins / metabolism
  • Cell Membrane / metabolism
  • Disulfides / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins* / chemistry
  • Lipopolysaccharides / metabolism
  • Lipoproteins / metabolism
  • Oxidative Stress


  • Escherichia coli Proteins
  • Lipopolysaccharides
  • Bacterial Outer Membrane Proteins
  • Disulfides
  • Lipoproteins
  • LptE protein, E coli