Ligand-gated diffusion across the bacterial outer membrane

Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10121-6. doi: 10.1073/pnas.1018532108. Epub 2011 May 18.

Abstract

Ligand-gated channels, in which a substrate transport pathway is formed as a result of the binding of a small-molecule chemical messenger, constitute a diverse class of membrane proteins with important functions in prokaryotic and eukaryotic organisms. Despite their widespread nature, no ligand-gated channels have yet been found within the outer membrane (OM) of Gram-negative bacteria. Here we show, using in vivo transport assays, intrinsic tryptophan fluorescence and X-ray crystallography, that high-affinity (submicromolar) substrate binding to the OM long-chain fatty acid transporter FadL from Escherichia coli causes conformational changes in the N terminus that open up a channel for substrate diffusion. The OM long-chain fatty acid transporter FadL from E. coli is a unique paradigm for OM diffusion-driven transport, in which ligand gating within a β-barrel membrane protein is a prerequisite for channel formation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacterial Outer Membrane Proteins / chemistry*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Biological Transport / physiology
  • Cell Membrane / metabolism*
  • Cell Membrane / ultrastructure
  • Crystallography, X-Ray
  • Diffusion
  • Escherichia coli / cytology*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Fatty Acid Transport Proteins / chemistry*
  • Fatty Acid Transport Proteins / genetics
  • Fatty Acid Transport Proteins / metabolism*
  • Fatty Acids / chemistry
  • Fatty Acids / metabolism
  • Ligand-Gated Ion Channels / chemistry*
  • Ligand-Gated Ion Channels / genetics
  • Ligand-Gated Ion Channels / metabolism*
  • Ligands*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation

Substances

  • Bacterial Outer Membrane Proteins
  • Escherichia coli Proteins
  • Fatty Acid Transport Proteins
  • Fatty Acids
  • Ligand-Gated Ion Channels
  • Ligands
  • fadL protein, E coli

Associated data

  • PDB/2R89
  • PDB/2R8A
  • PDB/3PF1
  • PDB/3PGR
  • PDB/3PGS
  • PDB/3PGU