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
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Research Support, N.I.H., Extramural
MeSH terms
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Bacterial Outer Membrane Proteins / chemistry*
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Bacterial Outer Membrane Proteins / genetics
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Bacterial Outer Membrane Proteins / metabolism*
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Biological Transport / physiology
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Cell Membrane / metabolism*
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Cell Membrane / ultrastructure
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Crystallography, X-Ray
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Diffusion
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Escherichia coli / cytology*
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Escherichia coli / metabolism
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Escherichia coli Proteins / chemistry*
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Escherichia coli Proteins / genetics
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Escherichia coli Proteins / metabolism*
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Fatty Acid Transport Proteins / chemistry*
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Fatty Acid Transport Proteins / genetics
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Fatty Acid Transport Proteins / metabolism*
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Fatty Acids / chemistry
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Fatty Acids / metabolism
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Ligand-Gated Ion Channels / chemistry*
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Ligand-Gated Ion Channels / genetics
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Ligand-Gated Ion Channels / metabolism*
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Ligands*
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Models, Molecular
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Molecular Sequence Data
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Protein Conformation
Substances
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Bacterial Outer Membrane Proteins
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Escherichia coli Proteins
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Fatty Acid Transport Proteins
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Fatty Acids
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Ligand-Gated Ion Channels
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Ligands
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fadL protein, E coli
Associated data
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PDB/2R89
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PDB/2R8A
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PDB/3PF1
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PDB/3PGR
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PDB/3PGS
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PDB/3PGU