title: A conserved structural motif for lipopolysaccharide recognition by procaryotic and eucaryotic proteins.
abstract: BACKGROUND
  Lipopolysaccharide (LPS), a lipoglycan from the outer membrane of Gram-negative bacteria, is an immunomodulatory molecule that stimulates the innate immune response. High levels of LPS cause excessive release of inflammatory mediators and are responsible for the septic shock syndrome. The interaction of LPS with its cognate binding proteins has not, as yet, been structurally elucidated.
  
  
  RESULTS
  The X-ray crystallographic structure of LPS in complex with the integral outer membrane protein FhuA from Escherichia coli K-12 is reported. It is in accord with data obtained using mass spectroscopy and nuclear magnetic resonance. Most of the important hydrogen-bonding or electrostatic interactions with LPS are provided by eight positively charged residues of FhuA. Residues in a similar three-dimensional arrangement were searched for in all structurally known proteins using a fast template-matching algorithm, and a subset of four residues was identified that is common to known LPS-binding proteins.
  
  
  CONCLUSIONS
  These four residues, three of which form specific interactions with lipid A, appear to provide the structural basis of pattern recognition in the innate immune response. Their arrangement can serve to identify LPS-binding sites on proteins known to interact with LPS, and could serve as a template for molecular modeling of a LPS scavenger designed to reduce the septic shock syndrome.
authors.affiliation: Fakultät für Biologie, Universität Konstanz, Konstanz, Germany.
authors.forename: A D
authors.initials: AD
authors.lastname: Ferguson
authors.forename: W
authors.initials: W
authors.lastname: Welte
authors.forename: E
authors.initials: E
authors.lastname: Hofmann
authors.forename: B
authors.initials: B
authors.lastname: Lindner
authors.forename: O
authors.initials: O
authors.lastname: Holst
authors.forename: J W
authors.initials: JW
authors.lastname: Coulton
authors.forename: K
authors.initials: K
authors.lastname: Diederichs
mesh_terms: D000209:Acute-Phase Proteins; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002240:Carbohydrate Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry; D029968:Escherichia coli Proteins; D006801:Humans; D006860:Hydrogen Bonding; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000378:metabolism*; D013058:Mass Spectrometry; D008562:Membrane Glycoproteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D000099231:Lipopolysaccharide-Binding Protein; C050900:FhuA protein, E coli