Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan

Science. 2003 Jun 6;300(5625):1584-7. doi: 10.1126/science.1084677.

Abstract

Although the role of Toll-like receptors in extracellular bacterial sensing has been investigated intensively, intracellular detection of bacteria through Nod molecules remains largely uncharacterized. Here, we show that human Nod1 specifically detects a unique diaminopimelate-containing N-acetylglucosamine-N-acetylmuramic acid (GlcNAc-MurNAc) tripeptide motif found in Gram-negative bacterial peptidoglycan, resulting in activation of the transcription factor NF-kappaB pathway. Moreover, we show that in epithelial cells (which represent the first line of defense against invasive pathogens), Nod1is indispensable for intracellular Gram-negative bacterial sensing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Motifs
  • Animals
  • Antigens, Differentiation / metabolism
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cell Line
  • Cytoplasm / microbiology
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Gram-Negative Bacteria / chemistry*
  • Gram-Negative Bacteria / immunology
  • Gram-Positive Bacteria / chemistry
  • Gram-Positive Bacteria / immunology
  • Humans
  • Immunity, Innate
  • Interleukin-8 / metabolism
  • Intracellular Signaling Peptides and Proteins*
  • Lipopolysaccharides / pharmacology
  • Mice
  • Myeloid Differentiation Factor 88
  • NF-kappa B / chemistry
  • NF-kappa B / metabolism
  • Nod1 Signaling Adaptor Protein
  • Nod2 Signaling Adaptor Protein
  • Oligopeptides / analysis*
  • Oligopeptides / chemistry
  • Peptidoglycan / chemistry*
  • Peptidoglycan / pharmacology
  • Protein Structure, Tertiary
  • Receptors, Immunologic / metabolism
  • Signal Transduction
  • Trisaccharides / analysis*
  • Trisaccharides / chemistry

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Carrier Proteins
  • GM-tripeptide, Neisseria meningitidis
  • Interleukin-8
  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • MYD88 protein, human
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • NOD1 protein, human
  • NOD2 protein, human
  • Nod1 Signaling Adaptor Protein
  • Nod2 Signaling Adaptor Protein
  • Oligopeptides
  • Peptidoglycan
  • Receptors, Immunologic
  • Trisaccharides