PDBsum entry 3dwn

Lipid transport

PDB id: 3dwn

Contents

Protein chains

421 a.a. *

Ligands

LDA ×6

Waters ×105

* Residue conservation analysis

PDB id:

3dwn

Name:

Lipid transport

Title:

Crystal structure of the long-chain fatty acid transporter fadl mutant a77e/s100r

Structure:

Long-chain fatty acid transport protein. Chain: a, b. Synonym: outer membrane fadl protein, outer membrane flp protein. Engineered: yes. Mutation: yes

Source:

Escherichia coli. Organism_taxid: 83333. Strain: k12. Gene: fadl, ttr, b2344, jw2341. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.50Å R-factor: 0.239 R-free: 0.289

Authors:

E.M.Hearn,D.R.Patel,B.W.Lepore,M.Indic,B.Van Den Berg

Key ref:

E.M.Hearn et al. (2009). Transmembrane passage of hydrophobic compounds through a protein channel wall. Nature, 458, 367-370. PubMed id: 19182779 DOI: 10.1038/nature07678

Date:

22-Jul-08 Release date: 16-Dec-08

Protein chains

P10384  (FADL_ECOLI) -  Long-chain fatty acid transport protein from Escherichia coli (strain K12)

Seq: 446 a.a.

Struc: 421 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1038/nature07678

Nature 458:367-370 (2009)

PubMed id: 19182779

Transmembrane passage of hydrophobic compounds through a protein channel wall.

E.M.Hearn, D.R.Patel, B.W.Lepore, M.Indic, B.van den Berg.

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.

Selected figure(s)

Figure 3.
Figure 3: A hydrophobic passageway for substrate diffusion in PaFadL. a, Superposition of EcFadL (green) and PaFadL (red), showing the conservation of the lateral opening. b, Superposition of the hatch domains. c, Stereo side view of PaFadL, with the three bound C[8]E[4] detergent molecules indicated in red. 2F[o]-F[c] density is shown as a blue mesh, contoured at 2.0 . The hatch domain is coloured green. The belts of aromatic residues that delineate the polar–apolar interfaces of the outer membrane are shown as orange stick models.

Figure 4.
Figure 4: Proposed lateral diffusion model for the uptake of hydrophobic substrates by FadL proteins. a, Substrate (red hexagon) capture from the extracellular medium by a low-affinity binding site (L)^15; b, diffusion of the substrate into an adjacent high-affinity binding site H (blue)^15; c, spontaneous conformational changes in the N terminus (purple) result in substrate release and create a continuous passageway to the barrel wall opening formed by the kink in strand S3. The substrate diffuses laterally through the opening into the outer membrane (OM). The polar part of the LPS, constituting the principal barrier in the transport process, is shown in grey. The extracellular milieu (E) is at the top and the periplasm (P) is at the bottom.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: Nature (2009, 458, 367-370) copyright 2009.

Figures were selected by an automated process.