Siderophore-Mediated Iron Transport: Crystal Structure of FhuA with Bound Lipopolysaccharide

• Published in: Science (American Association for the Advancement of Science) 1998-12, Vol.282 (5397), p.2215-2220
• Main Authors: Ferguson, Andrew D., Hofmann, Eckhard, Coulton, James W., Diederichs, Kay, Welte, Wolfram
• Format: Article
• Language: English
• Subjects: Active biological transport; Analytical, structural and metabolic biochemistry; Atoms; Bacteria; Bacterial Outer Membrane Proteins - chemistry; Bacterial Outer Membrane Proteins - metabolism; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Bacteriophages; Binding and carrier proteins; Binding Sites; Biological and medical sciences; Biological Transport, Active; Cell Membrane - chemistry; Cell Membrane - metabolism; Cell membranes; Crystallography; Crystallography, X-Ray; Diffusion; Elementary Secondary Education; Escherichia coli; Escherichia coli - chemistry; Escherichia coli - metabolism; Escherichia coli Proteins; Ferric Compounds - metabolism; Ferrichrome - metabolism; Fundamental and applied biological sciences. Psychology; Hydrogen Bonding; Iron; Iron (Nutrient); Iron in the body; Ligands; Lipopolysaccharides - metabolism; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Models, Molecular; Molecules; Periplasm; Physiological aspects; Porins; Protein Conformation; Protein Structure, Secondary; Proteins; Receptors; Receptors, Virus - chemistry; Receptors, Virus - metabolism; Scientific Concepts; Siderophores; Signal Transduction
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.282.5397.2215

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 β barrel composed of 22 antiparallel β strands. In contrast to the typical trimeric arrangement found in porins, FhuA is monomeric. Located within the β barrel is a structurally distinct domain, the "cork," which mainly consists of a four-stranded β sheet and four short α 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.