title: TonB-dependent receptors-structural perspectives.
abstract: Plants, bacteria, fungi, and yeast utilize organic iron chelators (siderophores) to establish commensal and pathogenic relationships with hosts and to survive as free-living organisms. In Gram-negative bacteria, transport of siderophores into the periplasm is mediated by TonB-dependent receptors. A complex of three membrane-spanning proteins TonB, ExbB and ExbD couples the chemiosmotic potential of the cytoplasmic membrane with siderophore uptake across the outer membrane. The crystallographic structures of two TonB-dependent receptors (FhuA and FepA) have recently been determined. These outer membrane transporters show a novel fold consisting of two domains. A 22-stranded antiparallel beta-barrel traverses the outer membrane and adjacent beta-strands are connected by extracellular loops and periplasmic turns. Located inside the beta-barrel is the plug domain, composed primarily of a mixed four-stranded beta-sheet and a series of interspersed alpha-helices. Siderophore binding induces distinct local and allosteric transitions that establish the structural basis of signal transduction across the outer membrane and suggest a transport mechanism.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9050, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Ferguson
authors.forename: Johann
authors.initials: J
authors.lastname: Deisenhofer
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000737:chemistry; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins / Q000737:chemistry; D006090:Gram-Negative Bacteria / Q000737:chemistry / Q000378:metabolism*; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019897:Periplasm / Q000378:metabolism; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism*; D011991:Receptors, Virus / Q000737:chemistry; D017262:Siderophores / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018528:ATP-Binding Cassette Transporters; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C050900:FhuA protein, E coli; D008024:Ligands; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D017262:Siderophores; C029489:enterobactin receptor; C035902:siderophore receptors; C057616:tonB protein, Bacteria; C489181:tonB protein, E coli; D007501:Iron