Identification of LPS-binding peptide fragment of MD-2, a toll-receptor accessory protein

Biochem Biophys Res Commun. 2002 Apr 12;292(4):880-5. doi: 10.1006/bbrc.2002.6748.

Abstract

Members of the toll-like receptor family are crucial in recognition of microbial pathogens as part of innate immune response. MD-2, an accessory protein to TLR4, present on the extracellular side of the membrane is needed to initiate the signal transduction. We have identified a 15 amino acid region of human MD-2 that contains several features of other lipopolysaccharide (LPS) binding proteins and peptides. In vitro LPS neutralization by this peptide was observed and confirmed by 2D transferred NOESY NMR experiments. NMR experiments have also shown binding of the MD-2 peptide to lipoteichoic acid (LTA) but not to peptidoglycan. Furthermore this peptide inhibited growth of gram-negative and to a lower extent of some gram-positive bacteria. Our results indicate that this region of MD-2 might be responsible for binding of LPS and confirms the role of MD-2 as an accessory protein in LPS signaling bestowing the Toll receptors their specificity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Surface / chemistry*
  • Antigens, Surface / metabolism
  • Binding Sites / physiology
  • Drosophila Proteins*
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / growth & development
  • Gram-Positive Bacteria / drug effects
  • Gram-Positive Bacteria / growth & development
  • Humans
  • Immunity, Innate / physiology
  • Lipopolysaccharides* / antagonists & inhibitors
  • Lipopolysaccharides* / metabolism
  • Lymphocyte Antigen 96
  • Magnetic Resonance Spectroscopy / methods
  • Membrane Glycoproteins / metabolism
  • Microbial Sensitivity Tests
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Peptidoglycan / metabolism
  • Protein Binding / physiology
  • Receptors, Cell Surface / metabolism
  • Signal Transduction / physiology
  • Teichoic Acids / metabolism
  • Toll-Like Receptor 4
  • Toll-Like Receptors

Substances

  • Antigens, Surface
  • Drosophila Proteins
  • LY96 protein, human
  • Lipopolysaccharides
  • Lymphocyte Antigen 96
  • Membrane Glycoproteins
  • Peptide Fragments
  • Peptidoglycan
  • Receptors, Cell Surface
  • TLR4 protein, human
  • Teichoic Acids
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • lipoteichoic acid