2R4O

Crystal structure of the long-chain fatty acid transporter FadL mutant delta NPA

Summary for 2R4O

• Entry DOI: 10.2210/pdb2r4o/pdb
• Related: 1T16 1T1L 2R4L 2R4M 2R4N 2R4P 2R88 2R89 2R8A 3DWN 3DWO
• Descriptor: Long-chain fatty acid transport protein, LAURYL DIMETHYLAMINE-N-OXIDE (2 entities in total)
• Functional Keywords: beta barrel, outer membrane protein, lipid transport, phage recognition, transmembrane, transport, transport protein
• Biological source: Escherichia coli
• Cellular location: Cell outer membrane; Multi-pass membrane protein: P10384
• Total number of polymer chains: 2
• Total formula weight: 94205.21

Authors

Hearn, E.M.,Patel, D.R.,Lepore, B.W.,Indic, M.,van den Berg, B. (deposition date: 2007-08-31, release date: 2008-09-16, Last modification date: 2023-08-30)

Primary citation

Hearn, E.M.,Patel, D.R.,Lepore, B.W.,Indic, M.,van den Berg, B.
Transmembrane passage of hydrophobic compounds through a protein channel wall
Nature, 458:367-370, 2009

PubMed Abstract: Membrane proteins that transport hydrophobic compounds have important roles in multi-drug resistance and can cause a number of diseases, underscoring the importance of protein-mediated transport of hydrophobic compounds. Hydrophobic compounds readily partition into regular membrane lipid bilayers, and their transport through an aqueous protein channel is energetically unfavourable. Alternative transport models involving acquisition from the lipid bilayer by lateral diffusion have been proposed for hydrophobic substrates. So far, all transport proteins for which a lateral diffusion mechanism has been proposed function as efflux pumps. Here we present the first example of a lateral diffusion mechanism for the uptake of hydrophobic substrates by the Escherichia coli outer membrane long-chain fatty acid transporter FadL. A FadL mutant in which a lateral opening in the barrel wall is constricted, but which is otherwise structurally identical to wild-type FadL, does not transport substrates. A crystal structure of FadL from Pseudomonas aeruginosa shows that the opening in the wall of the beta-barrel is conserved and delineates a long, hydrophobic tunnel that could mediate substrate passage from the extracellular environment, through the polar lipopolysaccharide layer and, by means of the lateral opening in the barrel wall, into the lipid bilayer from where the substrate can diffuse into the periplasm. Because FadL homologues are found in pathogenic and biodegrading bacteria, our results have implications for combating bacterial infections and bioremediating xenobiotics in the environment.

PubMed: 19182779
DOI: 10.1038/nature07678

Experimental method

X-RAY DIFFRACTION (3.6 Å)