title: Siderophore-mediated iron transport: crystal structure of FhuA with bound lipopolysaccharide.
abstract: FhuA, the receptor for ferrichrome-iron in Escherichia coli, is a member of a family of integral outer membrane proteins, which, together with the energy-transducing protein TonB, mediate the active transport of ferric siderophores across the outer membrane of Gram-negative bacteria. The three-dimensional structure of FhuA is presented here in two conformations: with and without ferrichrome-iron at resolutions of 2.7 and 2.5 angstroms, respectively. FhuA is a beta barrel composed of 22 antiparallel beta strands. In contrast to the typical trimeric arrangement found in porins, FhuA is monomeric. Located within the beta barrel is a structurally distinct domain, the "cork," which mainly consists of a four-stranded beta sheet and four short alpha helices. A single lipopolysaccharide molecule is noncovalently associated with the membrane-embedded region of the protein. Upon binding of ferrichrome-iron, conformational changes are transduced to the periplasmic pocket of FhuA, signaling the ligand-loaded status of the receptor. Sequence homologies and mutagenesis data are used to propose a structural mechanism for TonB-dependent siderophore-mediated transport across the outer membrane.
authors.affiliation: Department of Microbiology and Immunology, McGill University, 3775 University Street, Montreal, Quebec, Canada H3A 2B4.
authors.forename: A D
authors.initials: AD
authors.lastname: Ferguson
authors.forename: E
authors.initials: E
authors.lastname: Hofmann
authors.forename: J W
authors.initials: JW
authors.lastname: Coulton
authors.forename: K
authors.initials: K
authors.lastname: Diederichs
authors.forename: W
authors.initials: W
authors.lastname: Welte
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D001693:Biological Transport, Active; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D004058:Diffusion; D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D029968:Escherichia coli Proteins; D005290:Ferric Compounds / Q000378:metabolism*; D005291:Ferrichrome / Q000378:metabolism*; D006860:Hydrogen Bonding; D008024:Ligands; D008070:Lipopolysaccharides / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D005290:Ferric Compounds; C050900:FhuA protein, E coli; D008024:Ligands; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011991:Receptors, Virus; C057616:tonB protein, Bacteria; C489181:tonB protein, E coli; D005291:Ferrichrome