Structure of a proton-dependent lipid transporter involved in lipoteichoic acids biosynthesis

Nat Struct Mol Biol. 2020 Jun;27(6):561-569. doi: 10.1038/s41594-020-0425-5. Epub 2020 May 4.

Abstract

Lipoteichoic acids (LTAs) are essential cell-wall components in Gram-positive bacteria, including the human pathogen Staphylococcus aureus, contributing to cell adhesion, cell division and antibiotic resistance. Genetic evidence has suggested that LtaA is the flippase that mediates the translocation of the lipid-linked disaccharide that anchors LTA to the cell membrane, a rate-limiting step in S. aureus LTA biogenesis. Here, we present the structure of LtaA, describe its flipping mechanism and show its functional relevance for S. aureus fitness. We demonstrate that LtaA is a proton-coupled antiporter flippase that contributes to S. aureus survival under physiological acidic conditions. Our results provide foundations for the development of new strategies to counteract S. aureus infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Crystallography, X-Ray
  • Diglycerides / chemistry*
  • Disaccharides / chemistry
  • Hydrogen-Ion Concentration
  • Hydrophobic and Hydrophilic Interactions
  • Lipopolysaccharides / biosynthesis*
  • Magnetic Resonance Spectroscopy
  • Mutation
  • Protein Conformation
  • Protons
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / physiology*
  • Stress, Physiological
  • Teichoic Acids / biosynthesis*

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Diglycerides
  • Disaccharides
  • Lipopolysaccharides
  • Protons
  • Teichoic Acids
  • lipid transfer protein
  • lipoteichoic acid