Identification of LPS-binding peptide fragment of MD-2, a toll-receptor accessory protein.
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.
Mancek
Mateja
M
National Institute of Chemistry, Hajdrihova 19, Ljubljana, SI-1000, Slovenia.
Pristovsek
Primoz
P
Jerala
Roman
R
D000954:Antigens, Surface / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites / Q000502:physiology; D029721:Drosophila Proteins; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000378:metabolism; D051218:Lymphocyte Antigen 96; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008562:Membrane Glycoproteins / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010457:Peptidoglycan / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013682:Teichoic Acids / Q000378:metabolism; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D000954:Antigens, Surface; D029721:Drosophila Proteins; C495377:LY96 protein, human; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D010457:Peptidoglycan; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D013682:Teichoic Acids; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C009900:lipoteichoic acid