title: A CD14 domain with lipopolysaccharide-binding and -neutralizing activity.
abstract: The interaction of lipopolysaccharide with CD14 plays a key role in signaling that activates an early defense against pathogens but also contributes to the development of sepsis and septic shock. Here we have mapped the entire 356-amino-acid protein with synthetic 20-amino-acid peptides and have identified a new lipopolysaccharide-binding domain with a strong LPS-neutralizing activity. Moreover, analysis of the structure-activity relationship of this peptide, which corresponds to amino acids 81-100 of human CD14, revealed that leucines 87, 91, and 94 are essential for these activities. The functional relevance of these residues was confirmed by cellular expression of mutant CD14 proteins that are no longer able to bind LPS. Furthermore, the peptide provided a basis for the generation of highly soluble analogues with stronger lipopolysaccharide-neutralizing activity.
authors.affiliation: Institute for Cell Biology, Department of Molecular Biology, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany.
authors.forename: Söhnke
authors.initials: S
authors.lastname: Voss
authors.forename: Stefan
authors.initials: S
authors.lastname: Welte
authors.forename: Mariola
authors.initials: M
authors.lastname: Fotin-Mleczek
authors.forename: Rainer
authors.initials: R
authors.lastname: Fischer
authors.forename: Artur J
authors.initials: AJ
authors.lastname: Ulmer
authors.forename: Günther
authors.initials: G
authors.lastname: Jung
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Wiesmüller
authors.forename: Roland
authors.initials: R
authors.lastname: Brock
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D002942:Circular Dichroism; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
chemical_list: D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D010455:Peptides